1 Introduction
Catalytically active proteases are effectively blocked by their endogenous inhibitors under normal conditions. However, any change in level of synthesis and/or function of the proteases or their endogenous inhibitors may result in enzyme activity without inhibitory control. Uncontrolled proteolysis as a result of imbalance between active proteases and their endogenous inhibitors has been associated with different neuronal diseases, including brain tumors, stroke, some forms of epilepsy, Alzheimer's disease, and neurological autoimmune diseases. This chapter describes protease inhibitors and summarizes the current appreciation of their involvement in neurological disorders with particular emphasis on Alzheimer's disease (AD).
AD is characterized by the deposition of amyloid-β (Aβ) in the brain parenchyma and cerebral vessel walls, the formation of neurofibrillary tangles, and neuronal cell loss. These pathological characteristics are found also in patients with Down's...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abbink JJ, Nuijens JH, Eerenberg AJ, Huijbregts CC, Strack van Schijndel RJ, et al. 1991. Quantification of functional and inactivated α2-macroglobulin in sepsis. Thromb Haemost 65: 32–39.
Abraham CR, McGraw WT, Slot F, Yamin R. 2000. α1-antichymotrypsin inhibits Aβ degradation in vitro and in vivo. Ann N Y Acad Sci 920: 245–248.
Abraham CR, Potter H. 1989. The protease inhibitor, α1-antichymotrypsin, is a component of the brain amyloid deposits in normal aging and Alzheimer's disease. Ann Med 21: 77–81.
Abraham CR, Razzaboni BL, Sisodia SS, Koo EH, Price DL, et al. 1991. Studies on the proteolytic degradation of the β-protein precursor by proteases purified from Alzheimer's disease brain. Ann N Y Acad Sci 640: 161–165.
Abraham CR, Selkoe DJ, Potter H, Price DL, Cork LC. 1989. α1-antichymotrypsin is present together with the β-protein in monkey brain amyloid deposits. Neuroscience 32: 715–720.
Abraham CR, Shirahama T, Potter H. 1990. α1-antichymotrypsin is associated solely with amyloid deposits containing the β-protein. Amyloid and cell localization of α1-antichymotrypsin. Neurobiol Aging 11: 123–129.
Abrahamson M, Alvarez-Fernandez M, Nathanson CM. 2003. Cystatins. Biochem Soc Symp 179-199.
Abrahamson M, Buttle DJ, Mason RW, Hansson H, Grubb AO, et al. 1991. Regulation of cystatin C activity by serine proteinases. Biomed Biochim Acta 50: 587–593.
Abrahamson M, Grubb AO. 1994. Increased body temperature accelerates aggregation of the Leu-68→Gln mutant cystatin C, the amyloid-forming protein in hereditary cystatin C amyloid angiopathy. Proc Natl Acad Sci USA 91: 1416–1420.
Abrahamson M, Islam MQ, Szpirer J, Szpirer C, Levan G. 1989. The human cystatin C gene (CST3), mutated in hereditary cystatin C amyloid angiopathy, is located on chromosome 20. Hum Genet 82: 223–226.
Abrahamson M, Olafsson I, Palsdottir A, Ulvsback M, Lundwall A, et al. 1990. Structure and expression of the human cystatin C gene. Biochem J 268: 287–294.
Adair JC, Charlie J, Dencoff JE, Kaye JA, Quinn JF, et al. 2004. Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer's disease. Stroke 35: e159–162.
Aghajanyan HG, Arzumanyan AM, Arutunyan AA, Akopyan TN. 1988. Cystatins from bovine brain: Purification, some properties, and action on substance P degrading activity. Neurochem Res 13: 721–727.
Agostoni A, Cugno M. 2001. The kinin system: Biological mechanisms and clinical implications. Recenti Prog Med 92: 764–773.
Akira S, Hirano T, Taga T, Kishimoto T. 1990. Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF). FASEB J 4: 2860–2867.
Akopyan T. 1991. Protein inhibitors of proteinases from brain. Neurochem Res 16: 513–517.
Aksenova MV, Aksenov MY, Butterfield DA, Carney JM. 1996. α1-antichymotrypsin interaction with Aβ(1–40) inhibits fibril formation but does not affect the peptide toxicity. Neurosci Lett 211: 45–48.
Aksenov MY, Aksenova MV, Carney JM, Butterfield DA. 1996. α1-antichymotrypsin interaction with Aβ(1–42) does not inhibit fibril formation but attenuates the peptide toxicity. Neurosci Lett 217: 117–120.
Alakurtti K, Virtaneva K, Joensuu T, Palvimo JJ, Lehesjoki AE. 2000. Characterization of the cystatin B gene promoter harboring the dodecamer repeat expanded in progressive myoclonus epilepsy, EPM1. Gene 242: 65–73.
Albini A, Melchiori A, Santi L, Liotta LA, Brown PD, et al. 1991. Tumor cell invasion inhibited by TIMP-2. J Natl Cancer Inst 83: 775–779.
Alkemade JA, Molhuizen HO, Ponec M, Kempenaar JA, Zeeuwen PL, et al. 1994. SKALP/elafin is an inducible proteinase inhibitor in human epidermal keratinocytes. J Cell Sci 107 (Pt 8): 2335–2342.
Alvarez OA, Carmichael DF, De Clerck YA. 1990. Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. J Natl Cancer Inst 82: 589–595.
Alvarez-Fernandez M, Liang YH, Abrahamson M, Su XD. 2005. Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile. J Biol Chem 280: 18221–18228.
Apelt J, Ach K, Schliebs R. 2003. Aging-related downregulation of neprilysin, a putative β-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of β-amyloid plaques. Neurosci Lett 339: 183–186.
Apodaca G, Rutka JT, Bouhana K, Berens ME, Giblin JR, et al. 1990. Expression of metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cells. Cancer Res 50: 2322–2329.
Arai M, Goto T, Seichi A, Nakamura K. 2004. Effects of antithrombin III on spinal cord-evoked potentials and functional recovery after spinal cord injury in rats. Spine 29: 405–412.
Araki W, Kitaguchi N, Tokushima Y, Ishii K, Aratake H, et al. 1991. Trophic effect of β-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 181: 265–271.
Arnason A. 1935. Apoplexie und ihre Vererbung. Acta Psychiatr Neurol Scand (Suppl) VII: 1–180.
Aronica E, van Vliet EA, Hendriksen E, Troost D, Lopes da Silva FH, et al. 2001. Cystatin C, a cysteine protease inhibitor, is persistently upregulated in neurons and glia in a rat model for mesial temporal lobe epilepsy. Eur J Neurosci 14: 1485–1491.
Assfalg-Machleidt I, Jochum M, Nast-Kolb D, Siebeck M, Billing A, et al. 1990. Cathepsin-B indicator for the release of lysosomal cysteine proteinases in severe trauma and inflammation. Biol Chem Hoppe-Seyler 371: 211–222.
Banks RE, Evans SW, Alexander D, Van Leuven F, Whicher JT, et al. 1991. α2-macroglobulin state in acute pancreatitis. Raised values of α2-macroglobulin–protease complexes in severe and mild attacks. Gut 32: 430–434.
Bannerman DD, Sathyamoorthy M, Goldblum SE. 1998. Bacterial lipopolysaccharide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins. J Biol Chem 273: 35371–35380.
Barker-Carlson K, Lawrence DA, Schwartz BS. 2002. Acyl-enzyme complexes between tissue-type plasminogen activator and neuroserpin are short-lived in vitro. J Biol Chem 277: 46852–46857.
Barrett A, Rawlings N, Davies M, Machleidt W, Salvesen G, Turk V. 1986. Cysteine proteinase inhibitors of the cystatin superfamily. Proteinase inhibitors. Barrett AJ, Salvesen GS, editors. Amsterdam: Elsevier.
Barrett AJ. 1986. The cystatins: a diverse superfamily of cysteine peptidase inhibitors. Biomed Biochim Acta 45: 1363–1374.
Barrett AJ, Fritz H, Grubb A, Isemura S, Jarvinen M, et al. 1986. Nomenclature and classification of the proteins homologous with the cysteine proteinase inhibitor chicken cystatin. Biochem J 236: 312
Belorgey D, Crowther DC, Mahadeva R, Lomas DA. 2002. Mutant neuroserpin (S49P) that causes familial encephalopathy with neuroserpin inclusion bodies is a poor proteinase inhibitor and readily forms polymers in vitro. J Biol Chem 277: 17367–17373.
Belorgey D, Sharp LK, Crowther DC, Onda M, Johansson J, et al. 2004. Neuroserpin portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymers: Implications for the epilepsy seen in the dementia FENIB. Eur J Biochem 271: 3360–3367.
Benedikz E, Blondal H, Gudmundsson G. 1990. Skin deposits in hereditary cystatin C amyloidosis. Virchows Arch A Pathol Anat Histopathol 417: 325–331.
Benussi L, Ghidoni R, Steinhoff T, Alberici A, Villa A, et al. 2003. Alzheimer's disease-associated cystatin C variant undergoes impaired secretion. Neurobiol Dis 13: 15–21.
Bernstein HG, Kirschke H, Wiederanders B, Pollak KH, Zipress A, et al. 1996. The possible place of cathepsins and cystatins in the puzzle of Alzheimer's disease: a review. Mol Chem Neuropathol 27: 225–247.
Bernstein HG, Rinne R, Kirschke H, Jarvinen M, Knofel B, et al. 1994. Cystatin A-like immunoreactivity is widely distributed in human brain and accumulates in neuritic plaques of Alzheimer's disease subjects. Brain Res Bull 33: 477–481.
Berti PJ, Storer AC. 1995. Alignment/phylogeny of the papain superfamily of cysteine proteases. J Mol Biol 246: 273–283.
Bever CT Jr, Garver DW. 1995. Increased cathepsin B activity in multiple sclerosis brain. J Neurol Sci 131: 71–73.
Beyer K, Lao JI, Gomez M, Riutort N, Latorre P, et al. 2001. Alzheimer's disease and the cystatin C gene polymorphism: an association study. Neurosci Lett 315: 17–20.
Bi X, Yong AP, Zhou J, Gall CM, Lynch G. 2000. Regionally selective changes in brain lysosomes occur in the transition from young adulthood to middle age in rats. Neuroscience 97: 395–404.
Bidere N, Lorenzo HK, Carmona S, Laforge M, Harper F, et al. 2003. Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278: 31401–31411.
Bird PI. 1998. Serpins and regulation of cell death. Results Probl Cell Differ 24: 63–89.
Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, et al. 1993. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4: 197–250.
Black RA, Kronheim SR, Sleath PR. 1989. Activation of interleukin-1β by a coinduced protease. FEBS Lett 247: 386–390.
Blaukat A. 2003. Structure and signaling pathways of kinin receptors. Andrologia 35: 17–23.
Bleuel A, de Gasparo M, Whitebread S, Puttner I, Monard D. 1995. Regulation of protease nexin-1 expression in cultured Schwann cells is mediated by angiotensin II receptors. J Neurosci 15: 750–761.
Bobek LA, Levine MJ. 1992. Cystatins—inhibitors of cysteine proteinases. Crit Rev Oral Biol Med 3: 307–332.
Bode W, Huber R. 1991. Proteinase–protein inhibitor interaction. Biomed Biochim Acta 50: 437–446.
Bode W, Huber R. 1992. Natural protein proteinase inhibitors and their interaction with proteinases. Eur J Biochem 204: 433–451.
Boike G, Lah T, Sloane BF, Rozhin J, Honn K, et al. 1992. A possible role for cysteine proteinase and its inhibitors in motility of malignant melanoma and other tumour cells. Melanoma Res 1: 333–340.
Boland B, Campbell V. 2004. Aβ-mediated activation of the apoptotic cascade in cultured cortical neurones: a role for cathepsin-L. Neurobiol Aging 25: 83–91.
Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, et al. 1997. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19: 939–945.
Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, et al. 1996. Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ(1–42/1—40) ratio in vitro and in vivo. Neuron 17: 1005–1013.
Borg M, Ruchel R. 1988. Expression of extracellular acid proteinase by proteolytic Candida spp. during experimental infection of oral mucosa. Infect Immun 56: 626–631.
Borth W. 1992. α2-macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J 6: 3345–3353.
Brannvall K, Hjelm H, Korhonen L, Lahtinen U, Lehesjoki AE, et al. 2003. Cystatin-B is expressed by neural stem cells and by differentiated neurons and astrocytes. Biochem Biophys Res Commun 308: 369–374.
Breen KC, Bruce M, Anderton BH. 1991. β-amyloid precursor protein mediates neuronal cell–cell and cell–surface adhesion. J Neurosci Res 28: 90–100.
Briand C, Kozlov SV, Sonderegger P, Grutter MG. 2001. Crystal structure of neuroserpin: a neuronal serpin involved in a conformational disease. FEBS Lett 505: 18–22.
Briozzo P, Morisset M, Capony F, Rougeot C, Rochefort H. 1988. In vitro degradation of extracellular matrix with M r 52,000 cathepsin D secreted by breast cancer cells. Cancer Res 48: 3688–3692.
Broome D, Petanceska S. 2001. Papain-like cysteine proteases and their implications in neurodegenerative diseases. Role of proteases in the pathophysiology of neurodegenerative diseases. Lajtha A, Banik N, editors. New York: Kluwer Academic/Plenum Publishers; pp. 47–61.
Brown LR, De Marco A, Richarz R, Wagner G, Wuthrich K. 1978. The influence of a single salt bridge on static and dynamic features of the globular solution conformation of the basic pancreatic trypsin inhibitor. 1H and 13C nuclear magnetic resonance studies of the native and the transaminated inhibitor. Eur J Biochem 88: 87–95.
Buck MR, Karustis DG, Day NA, Honn KV, Sloane BF. 1992. Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. Biochem J. 282 (Pt 1): 273–278.
Buisson A, Nicole O, Docagne F, Sartelet H, Mackenzie ET, et al. 1998. Upregulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1. FASEB J 12: 1683–1691.
Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, et al. 1992. Assembly and aggregation properties of synthetic Alzheimer's A4/β-amyloid peptide analogs. J Biol Chem 267: 546–554.
Buttle DJ, Abrahamson M, Burnett D, Mort JS, Barrett AJ, et al. 1991. Human sputum cathepsin B degrades proteoglycan, is inhibited by α2-macroglobulin, and is modulated by neutrophil elastase cleavage of cathepsin B precursor and cystatin C. Biochem J 276: 325–331.
Cai XD, Golde TE, Younkin SG. 1993. Release of excess amyloid-β protein from a mutant amyloid-β protein precursor. Science 259: 514–516.
Caille I, Allinquant B, Dupont E, Bouillot C, Langer A, et al. 2004. Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Development 131: 2173–2181.
Calkins CC, Sloane BF. 1995. Mammalian cysteine protease inhibitors: Biochemical properties and possible roles in tumor progression. Biol Chem Hoppe Seyler 376: 71–80.
Carrell RW, Lomas DA. 2002. α1-antitrypsin deficiency—a model for conformational diseases. N Engl J Med 346: 45–53.
Cataldo AM, Barnett JL, Berman SA, Li J, Quarless S, et al. 1995. Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: Evidence for early upregulation of the endosomal–lysosomal system. Neuron 14: 671–680.
Cataldo AM, Hamilton DJ, Barnett JL, Paskevich PA, Nixon RA. 1996. Properties of the endosomal–lysosomal system in the human central nervous system: Disturbances mark most neurons in populations at risk to degenerate in Alzheimer's disease. J Neurosci 16: 186–199.
Cataldo AM, Hamilton DJ, Nixon RA. 1994. Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer's disease. Brain Res 640: 68–80.
Cataldo AM, Nixon RA. 1990. Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain. Proc Natl Acad Sci USA 87: 3861–3865.
Cataldo AM, Thayer CY, Bird ED, Wheelock TR, Nixon RA. 1990. Lysosomal proteinase antigens are prominently localized within senile plaques of Alzheimer's disease: Evidence for a neuronal origin. Brain Res 513: 181–192.
Cawston TE. 1995. Proteinases and inhibitors. Br Med Bull 51: 385–401.
Chambers AF, Matrisian LM. 1997. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89: 1260–1270.
Chang DI, Hosomi N, Lucero J, Heo JH, Abumiya T, et al. 2003. Activation systems for latent matrix metalloproteinase-2 are upregulated immediately after focal cerebral ischemia. J Cereb Blood Flow Metab 23: 1408–1419.
Chapman HA Jr, Reilly JJ Jr, Yee R, Grubb AO. 1990. Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. Am Rev Respir Dis 141: 698–705.
Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, et al. 1991. Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 353: 844–846.
Chaudhuri L. 1993. Human α2-macroglobulin and its biological significance. Indian J Exp Biol 31: 723–727.
Cheung PP, Cannizzaro LA, Colman RW. 1992. Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter. Cytogenet Cell Genet 59: 24–26.
Choi BH, Suzuki M, Kim T, Wagner SL, Cunningham DD. 1990. Protease nexin-1. Localization in the human brain suggests a protective role against extravasated serine proteases. Am J Pathol 137: 741–747.
Chu CT, Pizzo SV. 1994. α2-Macroglobulin, complement, and biologic defense: antigens, growth factors, microbial proteases, and receptor ligation. Lab Invest 71: 792–812.
Cinelli P, Madani R, Tsuzuki N, Vallet P, Arras M, et al. 2001. Neuroserpin, a neuroprotective factor in focal ischemic stroke. Mol Cell Neurosci 18: 443–457.
Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, et al. 1992. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β protein production. Nature 360: 672–674.
Citron M, Westaway D, Xia W, Carlson G, Diehl T, et al. 1997. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nat Med 3: 67–72.
Clarimon J, Munoz FJ, Boada M, Tarraga L, Sunyer J, et al. 2003. Possible increased risk for Alzheimer's disease associated with neprilysin gene. J Neural Transm 110: 651–657.
Cohen DH, Feiner H, Jensson O, Frangione B. 1983. Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastrentero-pancreatic neuroendocrine protein, γ trace. J Exp Med 158: 623–628.
Cornwall GA, Hsia N. 2002. Cres (cystatin-related epididymal spermatogenic) gene regulation and function. Zhonghua Nan Ke Xue 8: 313–318.
Costello PC, Del Maestro RF, Stetler-Stevenson WG. 1994. Gelatinase A expression in human malignant gliomas. Ann N Y Acad Sci 732: 450–452.
Crawford FC, Freeman MJ, Schinka JA, Abdullah LI, Gold M, et al. 2000. A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease. Neurology 55: 763–768.
Creighton TE, Charles IG. 1987. Biosynthesis, processing, and evolution of bovine pancreatic trypsin inhibitor. Cold Spring Harb Symp Quant Biol 52: 511–519.
Crisp RJ, Knauer MF, Knauer DJ. 2002. Protease nexin 1 is a potent urinary plasminogen activator inhibitor in the presence of collagen type IV. J Biol Chem 277: 47285–47291.
Damas J, Garbacki N, Lefebvre PJ. 2004. The kallikrein–kinin system, angiotensin converting enzyme inhibitors, and insulin sensitivity. Diabetes Metab Res Rev 20: 288–297.
Davis RL, Holohan PD, Shrimpton AE, Tatum AH, Daucher J, et al. 1999a. Familial encephalopathy with neuroserpin inclusion bodies. Am J Pathol 155: 1901–1913.
Davis RL, Shrimpton AE, Carrell RW, Lomas DA, Gerhard L, et al. 2002. Association between conformational mutations in neuroserpin and onset and severity of dementia. Lancet 359: 2242–2247.
Davis RL, Shrimpton AE, Holohan PD, Bradshaw C, Feiglin D, et al. 1999b. Familial dementia caused by polymerization of mutant neuroserpin. Nature 401: 376–379.
de Boer JP, Creasey AA, Chang A, Abbink JJ, Roem D, et al. 1993. α2-macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: Studies using a baboon model. Infect Immun 61: 5035–5043.
De Clerck YA, Darville MI, Eeckhout Y, Rousseau GG. 1994. Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2). Gene 139: 185–191.
De Clerck YA, Yean TD, Chan D, Shimada H, Langley KE. 1991. Inhibition of tumor invasion of smooth muscle cell layers by recombinant human metalloproteinase inhibitor. Cancer Res 51: 2151–2157.
De Jonghe C, Zehr C, Yager D, Prada CM, Younkin S, et al. 1998. Flemish and Dutch mutations in amyloid-β precursor protein have different effects on amyloid β secretion. Neurobiol Dis 5: 281–286.
DeLa Cadena RA, Colman RW. 1991. Structure and functions of human kininogens. Trends Pharmacol Sci 12: 272–275.
Delaisse JM, Ledent P, Vaes G. 1991. Collagenolytic cysteine proteinases of bone tissue. Cathepsin B, (pro)cathepsin L and a cathepsin L-like 70 kDa proteinase. Biochem J. 279 (Pt 1): 167–174.
Demchik LL, Sameni M, Nelson K, Mikkelsen T, Sloane BF. 1999. Cathepsin B and glioma invasion. Int J Dev Neurosci 17: 483–494.
Deng A, Irizarry MC, Nitsch RM, Growdon JH, Rebeck GW. 2001. Elevation of cystatin c in susceptible neurons in Alzheimer's disease. Am J Pathol 159: 1061–1068.
Denhardt DT, Feng B, Edwards DR, Cocuzzi ET, Malyankar UM. 1993. Tissue inhibitor of metalloproteinases (TIMP, aka EPA): Structure, control of expression, and biological functions. Pharmacol Ther 59: 329–341.
Docagne F, Nicole O, Marti HH, Mac Kenzie ET, Buisson A, et al. 1999. Transforming growth factor-β1 as a regulator of the serpins/t-PA axis in cerebral ischemia. FASEB J 13: 1315–1324.
Dodel RC, Du Y, Depboylu C, Kurz A, Eastwood B, et al. 2002. A polymorphism in the cystatin C promoter region is not associated with an increased risk of AD. Neurology 58: 664.
Downing MR, Bloom JW, Mann KG. 1978. Comparison of the inhibition of thrombin by three plasma protease inhibitors. Biochemistry 17: 2649–2653.
Du Y, Bales KR, Dodel RC, Liu X, Glinn MA, et al. 1998. α2-macroglobulin attenuates β-amyloid peptide 1–40 fibril formation and associated neurotoxicity of cultured fetal rat cortical neurons. J Neurochem 70: 1182–1188.
Duff K, Eckman C, Zehr C, Yu X, Prada CM, et al. 1996. Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1. Nature 383: 710–713.
Duffy MJ. 1996. Proteases as prognostic markers in cancer. Clin Cancer Res 2: 613–618.
Dziegielewska KM, Saunders NR, Schejter EJ, Zakut H, Zevin-Sonkin D, et al. 1986. Synthesis of plasma proteins in fetal, adult, and neoplastic human brain tissue. Dev Biol 115: 93–104.
Eckman EA, Reed DK, Eckman CB. 2001. Degradation of the Alzheimer's amyloid-β peptide by endothelin-converting enzyme. J Biol Chem 276: 24540–24548.
Ekiel I, Abrahamson M. 1996. Folding-related dimerization of human cystatin C. J Biol Chem 271: 1314–1321.
Ellis AJ, Curry VA, Powell EK, Cawston TE. 1994. The prevention of collagen breakdown in bovine nasal cartilage by TIMP, TIMP-2, and a low-molecular weight synthetic inhibitor. Biochem Biophys Res Commun 201: 94–101.
Ellis V, Scully M, Mac Gregor I, Kakkar V. 1982. Inhibition of human factor Xa by various plasma protease inhibitors. Biochim Biophys Acta 701: 24–31.
Eriksson S, Janciauskiene S, Lannfelt L. 1995. α1-antichymotrypsin regulates Alzheimer β-amyloid peptide fibril formation. Proc Natl Acad Sci USA 92: 2313–2317.
Evin G, Sharples RA, Weidemann A, Reinhard FB, Carbone V, et al. 2001. Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's disease. Biochemistry 40: 8359–8368.
Festoff BW, Suo Z, Citron BA. 2001. Plasticity and stabilization of neuromuscular and CNS synapses: interactions between thrombin protease signaling pathways and tissue transglutaminase. Int Rev Cytol 211: 153–177.
Finckh U, Kammer von Der H, Velden J, Michel T, Andresen B, et al. 2000. Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease. Arch Neurol 57: 1579–1583.
Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C. 2004. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol 48: 411–424.
Forsyth P, Edwards D, La Fleur M, Yong V. 2001. Proteases and their inhibitors in gliomas. Role of proteases in the pathophysiology of neurodegenerative diseases. Lajtha A, Banik N, editors. New York: Kluwer Academic/Plenum Publishers; pp. 214–268.
Forsyth PA, Laing TD, Gibson AW, Rewcastle NB, Brasher P, et al. 1998. High levels of gelatinase-B and active gelatinase-A in metastatic glioblastoma. J Neurooncol 36: 21–29.
Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, et al. 1999. Gelatinase-A (MMP-2), gelatinase-B (MMP-9), and membrane-type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79: 1828–1835.
Fraser PE, Nguyen JT, McLachlan DR, Abraham CR, Kirschner DA. 1993. α1-antichymotrypsin binding to Alzheimer Aβ peptides is sequence specific and induces fibril disaggregation in vitro. J Neurochem 61: 298–305.
Freije JP, Abrahamson M, Olafsson I, Velasco G, Grubb A, et al. 1991. Structure and expression of the gene encoding cystatin D, a novel human cysteine proteinase inhibitor. J Biol Chem 266: 20538–20543.
Friedland RP. 2002. Lipid metabolism, epidemiology, and the mechanisms of Alzheimer's disease. Ann N Y Acad Sci 977: 387–390.
Fumagalli L, Businaro R, Nori SL, Pompili E, De Renzis G. 1999. Regulation of neurotrophic functions: Proteinase inhibitors. Ital J Anat Embryol 104: 53–88.
Gaddy-Kurten D, Richards JS. 1991. Regulation of α2-macroglobulin by luteinizing hormone and prolactin during cell differentiation in the rat ovary. Mol Endocrinol 5: 1280–1291.
Ganter U, Strauss S, Jonas U, Weidemann A, Beyreuther K, et al. 1991. α2-macroglobulin synthesis in interleukin-6-stimulated human neuronal (SH-SY5Y neuroblastoma) cells. Potential significance for the processing of Alzheimer β-amyloid precursor protein. FEBS Lett 282: 127–131.
Garton MJ, Keir G, Lakshmi MV, Thompson EJ. 1991. Age-related changes in cerebrospinal fluid protein concentrations. J Neurol Sci 104: 74–80.
Gettins P, Patston PA, Schapira M. 1993. The role of conformational change in serpin structure and function. Bioessays 15: 461–467.
Ghebremedhin E, Schultz C, Thal DR, Del Tredici K, Rueb U, et al. 2002. Genetic association of argyrophilic grain disease with polymorphisms in α2-macroglobulin and low-density lipoprotein receptor-related protein genes. Neuropathol Appl Neurobiol 28: 308–313.
Ghiso J, Pons-Estel B, Frangione B. 1986. Hereditary cerebral amyloid angiopathy: the amyloid fibrils contain a protein, which is a variant of cystatin C, an inhibitor of lysosomal cysteine proteases. Biochem Biophys Res Commun 136: 548–554.
Giraldi T, Nisi C, Sava G. 1977. Lysosomal enzyme inhibitors and antimetastatic activity in the mouse. Eur J Cancer 13: 1321–1323.
Giraudon P, Malcus C, Chalon A, Vincent P, Khuth S, et al. 2003. Astrocytes, cells involved in neuroimmune interactions in the central nervous system. J Soc Biol 197: 103–112.
Glenner GG, Wong CW. 1984. Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120: 885–890.
Goddard KA, Olson JM, Payami H, Voet Van Der M, Kuivaniemi H, et al. 2004. Evidence of linkage and association on chromosome 20 for late-onset Alzheimer's disease. Neurogenetics 5: 121–128.
Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, et al. 1991. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704–706.
Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC. 1987. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235: 877–878.
Gonias SL. 1992. α2-macroglobulin: a protein at the interface of fibrinolysis and cellular growth regulation. Exp Hematol 20: 302–311.
Graffagnino C, Herbstreith MH, Schmechel DE, Levy E, Roses AD, et al. 1995. Cystatin C mutation in an elderly man with sporadic amyloid angiopathy and intracerebral hemorrhage. Stroke 26: 2190–2193.
Grasbon-Frodl EM, Egensperger R, Kosel S, Kruger R, Riess O, et al. 1999. The α1-antichymotrypsin A-allele in German Parkinson's disease patients. J Neural Transm 106: 729–736.
Grinde B, Hungnes O, Tjotta E. 1989. The proteinase inhibitor pepstatin A inhibits formation of reverse transcriptase in H9 cells infected with human immunodeficiency virus 1. AIDS Res Hum Retroviruses 5: 269–274.
Gudmundsson G, Hallgrimsson J, Jonasson TA, Bjarnason O. 1972. Hereditary cerebral hemorrhage with amyloidosis. Brain 95: 387–404.
Haan J, Maat-Schieman MLC, van Duinen SG, Jensson O, Thorsteinsson L, et al. 1994. Colocalization of β/A4 and cystatin C in cortical blood vessels in Dutch, but not in Icelandic hereditary cerebral hemorrhage with amyloidosis. Acta Neurol Scand 89: 367–371.
Haines JL, Pritchard ML, Saunders AM, Schildkraut JM, Growdon JH, et al. 1996. No genetic effect of α1-antichymotrypsin in Alzheimer's disease. Genomics 33: 53–56.
Hamil KG, Liu Q, Sivashanmugam P, Yenugu S, Soundararajan R, et al. 2002. Cystatin 11: a new member of the cystatin type 2 family. Endocrinology 143: 2787–2796.
Hammani K, Blakis A, Morsette D, Bowcock AM, Schmutte C, et al. 1996. Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene. J Biol Chem 271: 25498–25505.
Hammond GL. 1990. Molecular properties of corticosteroid-binding globulin and the sex-steroid binding proteins. Endocr Rev 11: 65–79.
Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, et al. 1987. Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors. Proc Natl Acad Sci USA 84: 5153–5157.
Hastings GA, Coleman TA, Haudenschild CC, Stefansson S, Smith EP, et al. 1997. Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival. J Biol Chem 272: 33062–33067.
Helisalmi S, Hiltunen M, Vepsalainen S, Iivonen S, Mannermaa A, et al. 2004. Polymorphisms in neprilysin gene affect the risk of Alzheimer's disease in Finnish patients. J Neurol Neurosurg Psychiatry 75: 1746–1748.
Hellgren M, Egberg N, Eklund J. 1984. Blood coagulation and fibrinolytic factors and their inhibitors in critically ill patients. Intensive Care Med 10: 23–28.
Hendriksen H, Datson NA, Ghijsen WE, van Vliet EA, da Silva FH, et al. 2001. Altered hippocampal gene expression prior to the onset of spontaneous seizures in the rat poststatus epilepticus model. Eur J Neurosci 14: 1475–1484.
Hengst U, Albrecht H, Hess D, Monard D. 2001. The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J Biol Chem 276: 535–540.
Herz J, Clouthier DE, Hammer RE. 1992. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Cell 71: 411–421.
Hibbetts K, Hines B, Williams D. 1999. An overview of proteinase inhibitors. J Vet Intern Med 13: 302–308.
Hicks NJ, Ward RV, Reynolds JJ. 1984. A fibrosarcoma model derived from mouse embryo cells: Growth properties and secretion of collagenase and metalloproteinase inhibitor (TIMP) by tumour cell lines. Int J Cancer 33: 835–844.
Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuther K. 1991. Aggregation and secondary structure of synthetic amyloid-β A4 peptides of Alzheimer's disease. J Mol Biol 218: 149–163.
Hill IE, Preston E, Monette R, Mac Manus JP. 1997. A comparison of cathepsin B processing and distribution during neuronal death in rats following global ischemia or decapitation necrosis. Brain Res 751: 206–216.
Hill PA, Reynolds JJ, Meikle MC. 1993. Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2. Biochim Biophys Acta 1177: 71–74.
Hill RM, Coates LC, Parmar PK, Mezey E, Pearson JF, et al. 2002. Expression and functional characterization of the serine protease inhibitor neuroserpin in endocrine cells. Ann N Y Acad Sci 971: 406–415.
Hirose K, Okajima K, Uchiba M, Nakano KY, Utoh J, et al. 2004. Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses. Thromb Haemost 91: 162–170.
Hochwald GM, Pepe AJ, Thorbecke GJ. 1967. Trace proteins in biological fluids. IV. Physicochemical properties and sites of formation of γ trace and β trace proteins. Proc Soc Exp Med 124: 961–966.
Hoffmann MC, Nitsch C, Scotti AL, Reinhard E, Monard D. 1992. The prolonged presence of glia-derived nexin, an endogenous protease inhibitor, in the hippocampus after ischemia-induced delayed neuronal death. Neuroscience 49: 397–408.
Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, et al. 1998. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 4: 97–100.
Hong J, Yoshida K, Rosner MR. 2002. Characterization of a cysteine proteinase inhibitor induced during neuronal cell differentiation. J Neurochem 81: 922–934.
Hook VY, Hwang SR. 2002. Novel secretory vesicle serpins, endopin 1 and endopin 2: Endogenous protease inhibitors with distinct target protease specificities. Biol Chem 383: 1067–1074.
Hooper NM, Trew AJ, Parkin ET, Turner AJ. 2000. The role of proteolysis in Alzheimer's disease. Adv Exp Med Biol 477: 379–390.
Hopkins WE, Fukagawa NK, Sobel BE, Schneider DJ. 2000. Plasminogen activator inhibitor type-1 in adults with Down's syndrome and protection against macrovascular disease. Am J Cardiol 85: 784–786, A789.
Houenou LJ, D'Costa AP, Li L, Turgeon VL, Enyadike C, et al. 1999. Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons. J Comp Neurol 412: 506–514.
Houenou LJ, Turner PL, Li L, Oppenheim RW, Festoff BW. 1995. A serine protease inhibitor, protease nexin I, rescues motoneurons from naturally occurring and axotomy-induced cell death. Proc Natl Acad Sci USA 92: 895–899.
Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, et al. 2003. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht–Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol 56: 315–327.
Hsu SJ, Nagase H, Balmain A. 2004. Identification of fetuin-B as a member of a cystatin-like gene family on mouse chromosome 16 with tumor suppressor activity. Genome 47: 931–946.
Hua Y, Keep RF, Schallert T, Hoff JT, Xi G. 2003a. A thrombin inhibitor reduces brain edema, glioma mass, and neurological deficits in a rat glioma model. Acta Neurochir Suppl 86: 503–506.
Hua Y, Wu J, Keep RF, Hoff JT, Xi G. 2003b. Thrombin exacerbates brain edema in focal cerebral ischemia. Acta Neurochir 86: Suppl 163–166.
Hughes SR, Khorkova O, Goyal S, Knaeblein J, Heroux J, et al. 1998. α2-macroglobulin associates with β-amyloid peptide and prevents fibril formation. Proc Natl Acad Sci USA 95: 3275–3280.
Huh CG, Hakansson K, Nathanson CM, Thorgeirsson UP, Jonsson N, et al. 1999. Decreased metastatic spread in mice homozygous for a null allele of the cystatin C protease inhibitor gene. Mol Pathol 52: 332–340.
Hutchison DC. 1988. Natural history of α1-protease inhibitor deficiency. Am J Med 84: 3–12.
Hwang SR, Steineckert B, Yasothornsrikul S, Sei CA, Toneff T, et al. 1999. Molecular cloning of endopin 1, a novel serpin localized to neurosecretory vesicles of chromaffin cells. Inhibition of basic residue-cleaving proteases by endopin 1. J Biol Chem 274: 34164–34173.
Ikeda Y, Hayashi I, Kamoshita E, Yamazaki A, Endo H, et al. 2004. Host stromal bradykinin B2 receptor signaling facilitates tumor-associated angiogenesis and tumor growth. Cancer Res 64: 5178–5185.
Imber MJ, Pizzo SV. 1981. Clearance and binding of two electrophoretic “fast” forms of human α2-macroglobulin. J Biol Chem 256: 8134–8139.
Inaba Y, Ichikawa M, Inoue A, Itoh M, Kyogashima M, et al. 2001. Plasma thrombin–antithrombin III complex is associated with the severity of experimental autoimmune encephalomyelitis. J Neurol Sci 185: 89–93.
Ishimaru H, Ishikawa K, Ohe Y, Takahashi A, Maruyama Y. 1996. Cystatin C and apolipoprotein E immunoreactivities in CA1 neurons in ischemic gerbil hippocampus. Brain Res 709: 155–162.
Itoh Y, Nagase H. 1995. Preferential inactivation of tissue inhibitor of metalloproteinases-1 that is bound to the precursor of matrix metalloproteinase-9 (progelatinase B) by human neutrophil elastase. J Biol Chem 270: 16518–16521.
Itoh Y, Yamada M, Hayakawa M, Otomo E, Miyatake T. 1993. Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly. J Neurol Sci 116: 135–141.
Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, et al. 2000. Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nat Med 6: 143–150.
Janciauskiene S. 2001. Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles. Biochim Biophys Acta 1535: 221–235.
Janciauskiene S, Eriksson S, Wright HT. 1996. A specific structural interaction of Alzheimer's peptide Aβ1–42 with α1-antichymotrypsin. Nat Struct Biol 3: 668–671.
Janciauskiene S, Gerbord MC, Lindgren S. 1998. Effects of serpins on cholesterol crystallization in model bile. J Hepatol 29: 541–549.
Jarrett JT, Berger EP, Lansbury PT Jr. 1993. The carboxy terminus of the β-amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease. Biochemistry 32: 4693–4697.
Jarrett JT, Lansbury PT Jr. 1993. Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73: 1055–1058.
Jensen PE, Humle Jorgensen S, Datta P, Sorensen PS. 2004. Significantly increased fractions of transformed to total α2-macroglobulin concentrations in plasma from patients with multiple sclerosis. Biochim Biophys Acta 1690: 203–207.
Jochum M, Gippner-Steppert C, Machleidt W, Fritz H. 1994. The role of phagocyte proteinases and proteinase inhibitors in multiple organ failure. Am J Respir Crit Care Med 150: S123–130.
Kabanda A, Goffin E, Bernard A, Lauwerys R, van Ypersele de Strihou C. 1995. Factors influencing serum levels and peritoneal clearances of low molecular weight proteins in continuous ambulatory peritoneal dialysis. Kidney Int 48: 1946–1952.
Kagedal K, Zhao M, Svensson I, Brunk UT. 2001. Sphingosine-induced apoptosis is dependent on lysosomal proteases. Biochem J 359: 335–343.
Kalra J, Chaudhary AK, Prasad K. 1989. Role of oxygen free radicals and pH on the release of cardiac lysosomal enzymes. J Mol Cell Cardiol 21: 1125–1136.
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, et al. 1987. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733–736.
Karrer KM, Peiffer SL, Di Tomas ME. 1993. Two distinct gene subfamilies within the family of cysteine protease genes. Proc Natl Acad Sci USA 90: 3063–3067.
Katakai K, Shinoda M, Kabeya K, Watanabe M, Ohe Y, et al. 1997. Changes in distribution of cystatin C, apolipoprotein E, and ferritin in rat hypothalamus after hypophysectomy. J Neuroendocrinol 9: 247–253.
Kato T, Ito T, Imatani T, Minaguchi K, Saitoh E, et al. 2004. Cystatin SA, a cysteine proteinase inhibitor, induces interferon-γ expression in CD4+ T cells. Biol Chem 385: 419–422.
Khokha R, Zimmer MJ, Graham CH, Lala PK, Waterhouse P. 1992a. Suppression of invasion by inducible expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in B16-F10 melanoma cells. J Natl Cancer Inst 84: 1017–1022.
Khokha R, Zimmer MJ, Wilson SM, Chambers AF. 1992b. Upregulation of TIMP-1 expression in B16-F10 melanoma cells suppresses their metastatic ability in chick embryo. Clin Exp Metastasis 10: 365–370.
Khrestchatisky M, Jourquin J, Ogier C, Charton G, Bernard A, et al. 2003. Matrix metalloproteinases and their inhibitors, modulators of neuroimmune interactions and of pathophysiological processes in the nervous system. J Soc Biol 197: 133–144.
Kim JA, Tran ND, Wang SJ, Fisher MJ. 2003. Astrocyte regulation of human brain capillary endothelial fibrinolysis. Thromb Res 112: 159–165.
Kingham PJ, Pocock JM. 2001. Microglial secreted cathepsin B induces neuronal apoptosis. J Neurochem 76: 1475–1484.
Kirschke H, Barrett AJ, Rawlings ND. 1995. Lysosomal cysteine proteinases. Protein profile. Sheterline P, editor. London: Academic Press; p. 1587.
Kish SJ, Shannak K, Rajput A, Deck JH, Hornykiewicz O. 1992. Aging produces a specific pattern of striatal dopamine loss: Implications for the etiology of idiopathic Parkinson's disease. J Neurochem 58: 642–648.
Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H. 1988. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331: 530–532.
Kitamura N, Kitagawa H, Fukushima D, Takagaki Y, Miyata T, et al. 1985. Structural organization of the human kininogen gene and a model for its evolution. J Biol Chem 260: 8610–8617.
Konduri SD, Yanamandra N, Siddique K, Joseph A, Dinh DH, et al. 2002. Modulation of cystatin C expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene 21: 8705–8712.
Kos J, Lah TT. 1998. Cysteine proteinases and their endogenous inhibitors: Target proteins for prognosis, diagnosis, and therapy in cancer . Oncol Rep 5: 1349–1361.
Kos J, Werle B, Lah T, Brunner N. 2000. Cysteine proteinases and their inhibitors in extracellular fluids: Markers for diagnosis and prognosis in cancer. Int J Biol Markers 15: 84–89.
Koshizuka Y, Yamada T, Hoshi K, Ogasawara T, Chung UI, et al. 2003. Cystatin 10, a novel chondrocyte-specific protein, may promote the last steps of the chondrocyte differentiation pathway. J Biol Chem 278: 48259–48266.
Kostura MJ, Tocci MJ, Limjuco G, Chin J, Cameron P, et al. 1989. Identification of a monocyte specific preinterleukin-1β convertase activity. Proc Natl Acad Sci USA 86: 5227–5231.
Kounnas MZ, Moir RD, Rebeck GW, Bush AI, Argraves WS, et al. 1995. LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted β-amyloid precursor protein and mediates its degradation. Cell 82: 331–340.
Kovacs DM. 2000. α2-macroglobulin in late-onset Alzheimer's disease. Exp Gerontol 35: 473–479.
Kumada T, Hasegawa A, Iwasaki Y, Baba H, Ikenaka K. 2004. Isolation of cystatin C via functional cloning of astrocyte differentiation factors. Dev Neurosci 26: 68–76.
Kvajo M, Albrecht H, Meins M, Hengst U, Troncoso E, et al. 2004. Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. J Neurosci 24: 9734–9743.
Lafreniere RG, Rochefort DL, Chretien N, Rommens JM, Cochius JI, et al. 1997. Unstable insertion in the 5′-flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1. Nat Genet 15: 298–302.
Lah TT, Babnik J, Schiffmann E, Turk V, Skaleric U. 1993. Cysteine proteinases and inhibitors in inflammation: their role in periodontal disease. J Periodon 64: 485–491.
Lalioti MD, Antonarakis SE, Scott HS. 2003. The epilepsy, the protease inhibitor, and the dodecamer: Progressive myoclonus epilepsy, cystatin b, and a 12-mer repeat expansion. Cytogenet Genome Res 100: 213–223.
Lalioti MD, Scott HS, Antonarakis SE. 1999. Altered spacing of promoter elements due to the dodecamer repeat expansion contributes to reduced expression of the cystatin B gene in EPM1. Hum Mol Genet 8: 1791–1798.
Lalioti MD, Scott HS, Buresi C, Rossier C, Bottani A, et al. 1997. Dodecamer repeat expansion in cystatin B gene in progressive myoclonus epilepsy. Nature 386: 847–851.
Lalioti MD, Scott HS, Genton P, Grid D, Ouazzani R, et al. 1998. A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset. Am J Hum Genet 62: 842–847.
Lamb H, Christie J, Singleton AB, Leake A, Perry RH, et al. 1998. Apolipoprotein E and α1-antichymotrypsin polymorphism genotyping in Alzheimer's disease and in dementia with Lewy bodies. Distinctions between diseases. Neurology 50: 388–391.
Lammle B, Tran TH, Ritz R, Duckert F. 1984. Plasma prekallikrein, factor XII, antithrombin III, C1(-)-inhibitor and α2-macroglobulin in critically ill patients with suspected disseminated intravascular coagulation (DIC). Am J Clin Pathol 82: 396–404.
Lampert K, Machein U, Machein MR, Conca W, Peter HH, et al. 1998. Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors. Am J Pathol 153: 429–437.
Langerholc T, Zavasnik-Bergant V, Turk B, Turk V, Abrahamson M, et al. 2005. Inhibitory properties of cystatin F and its localization in U937 promonocyte cells. FEBS J 272: 1535–1545.
Laskowski M Jr, Kato I. 1980. Protein inhibitors of proteinases. Annu Rev Biochem 49: 593–626.
Lauer D, Reichenbach A, Birkenmeier G. 2001. α2-macroglobulin-mediated degradation of amyloid β1–42: a mechanism to enhance amyloid β catabolism. Exp Neurol 167: 385–392.
Lee KS, Frank S, Vanderklish P, Arai A, Lynch G. 1991. Inhibition of proteolysis protects hippocampal neurons from ischemia. Proc Natl Acad Sci USA 88: 7233–7237.
Lee MA, Palace J, Stabler G, Ford J, Gearing A, et al. 1999. Serum gelatinase B, TIMP-1, and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study. Brain 122 (Pt 2): 191–197.
Lehesjoki AE. 2003. Molecular background of progressive myoclonus epilepsy. EMBO J 22: 3473–3478.
Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, et al. 2003. Enhanced proteolysis of β-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40: 1087–1093.
Lenarcic B, Bevec T. 1998. Thyropins—new structurally related proteinase inhibitors. Biol Chem 379: 105–111.
Lenarcic B, Krasovec M, Ritonja A, Olafsson I, Turk V. 1991. Inactivation of human cystatin C and kininogen by human cathepsin D. FEBS Lett 280: 211–215.
Lenarcic B, Krizaj I, Zunec P, Turk V. 1996. Differences in specificity for the interactions of stefins A, B, and D with cysteine proteinases. FEBS Lett 395: 113–118.
Lerner UH, Grubb A. 1992. Human cystatin C, a cysteine proteinase inhibitor, inhibits bone resorption in vitro stimulated by parathyroid hormone and parathyroid hormone-related peptide of malignancy. J Bone Miner Res 7: 433–440.
Leto G, Tumminello FM, Gebbia N, Woynarowska B, Bernacki RJ. 1990. Antimetastatic activity of adriamycin in combinations with proteinase inhibitors in mice. Anticancer Res 10: 265–269.
Levkau B, Herren B, Koyama H, Ross R, Raines EW. 1998. Caspase-mediated cleavage of focal adhesion kinase pp125FAK and disassembly of focal adhesions in human endothelial cell apoptosis. J Exp Med 187: 579–586.
Levy E, Carman MD, Fernandez-Madrid IJ, Power MD, Lieberburg I, et al. 1990. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248: 1124–1126.
Levy E, Lopez-Otin C, Ghiso J, Geltner D, Frangione B. 1989. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med 169: 1771–1778.
Levy E, Sastre M, Kumar A, Gallo G, Piccardo P, Ghetti B, Tagliavini F. 2001. Codeposition of cystatin C with amyloid-β protein in the brain of Alzheimer's disease patients. J Neuropathol Exp Neurol 60: 94–104.
Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, et al. 1995. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269: 973–977.
Li Y, Friel PJ, McLean DJ, Griswold MD. 2003. Cystatin E1 and E2, new members of male reproductive tract subgroup within cystatin type 2 family. Biol Reprod 69: 489–500.
Li Y, Friel PJ, Robinson MO, McLean DJ, Griswold MD. 2002. Identification and characterization of testis- and epididymis-specific genes: Cystatin SC and cystatin TE-1. Biol Reprod 67: 1872–1880.
Li YM, Lai MT, Xu M, Huang Q, DiMuzio-Mower J, et al. 2000. Presenilin-1 is linked with γ-secretase activity in the detergent solubilized state. Proc Natl Acad Sci USA 97: 6138–6143.
Liebl DJ, Koo PH. 1993. Serotonin-activated α2-macroglobulin inhibits neurite outgrowth and survival of embryonic sensory and cerebral cortical neurons. J Neurosci Res 35: 170–182.
Liebl DJ, Koo PH. 1994. Monoamine-activated α2-macroglobulin inhibits choline acetyltransferase of embryonic basal forebrain neurons and reversal of the inhibition by NGF and BDNF but not NT-3. J Neurosci Res 38: 407–414.
Lin JJ, Yueh KC, Chang CY, Chen CH, Lin SZ. 2004. The homozygote AA genotype of the α1-antichymotrypsin gene may confer protection against early-onset Parkinson's disease in women. Parkinsonism Relat Disord 10: 469–473.
Lomas DA, Mahadeva R. 2002. α1-antitrypsin polymerization and the serpinopathies: Pathobiology and prospects for therapy. J Clin Invest 110: 1585–1590.
Lopes MB, Bogaev CA, Gonias SL, Vanden Berg SR. 1994. Expression of α2-macroglobulin receptor/low-density lipoprotein receptor-related protein is increased in reactive and neoplastic glial cells. FEBS Lett 338: 301–305.
Lopez-Sanchez N, Muller U, Frade JM. 2005. Lengthening of G2/mitosis in cortical precursors from mice lacking β-amyloid precursor protein. Neuroscience 130: 51–60.
Lukasiuk K, Pirttila TJ, Pitkanen A. 2002. Upregulation of cystatin C expression in the rat hippocampus during epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Epilepsia 43 Suppl 5: 137–145.
Luthi A, Putten H, Botteri FM, Mansuy IM, Meins M, et al. 1997. Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation. J Neurosci 17: 4688–4699.
Ma J, Brewer HB, Potter H. 1996. Alzheimer Aβ neurotoxicity: Promotion by antichymotrypsin, ApoE4; inhibition by Aβ-related peptides. Neurobiol Aging 17: 773–780.
Ma J, Yee A, Brewer HB Jr, Das S, Potter H. 1994. Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments. Nature 372: 92–94.
Mach L, Mort JS, Glossl J. 1994. Maturation of human procathepsin B. Proenzyme activation and proteolytic processing of the precursor to the mature proteinase, in vitro, are primarily unimolecular processes. J Biol Chem 269: 13030–13035.
Madani R, Kozlov S, Akhmedov A, Cinelli P, Kinter J, et al. 2003. Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin. Mol Cell Neurosci 23: 473–494.
Maruyama H, Izumi Y, Oda M, Torii T, Morino H, et al. 2001. Lack of an association between cystatin C gene polymorphisms in Japanese patients with Alzheimer's disease. Neurology 57: 337–339.
Maruyama K, Ikeda S, Ishihara T, Allsop D, Yanagisawa N. 1990. Immunohistochemical characterization of cerebrovascular amyloid in 46 autopsied cases using antibodies to β protein and cystatin C. Stroke 21: 397–403.
Mason RW. 1989. Interaction of lysosomal cysteine proteinases with α2-macroglobulin: Conclusive evidence for the endopeptidase activities of cathepsins B and H. Arch Biochem Biophys 273: 367–374.
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, et al. 1985. Amyloid plaque core protein in Alzheimer's disease and Down's syndrome. Proc Natl Acad Sci USA 82: 4245–4249.
Matrisian LM. 1992. The matrix-degrading metalloproteinases. Bioessays 14: 455–463.
Matsuzawa K, Fukuyama K, Hubbard SL, Dirks PB, Rutka JT. 1996. Transfection of an invasive human astrocytoma cell line with a TIMP-1 cDNA: Modulation of astrocytoma invasive potential. J Neuropathol Exp Neurol 55: 88–96.
Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, et al. 1993. Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein. Neuron 10: 243–254.
Mayeux R, Lee JH, Romas SN, Mayo D, Santana V, et al. 2002. Chromosome 12 mapping of late-onset Alzheimer's disease among Caribbean Hispanics. Am J Hum Genet 70: 237–243.
McCormick D. 1993. Secretion of cathepsin B by human gliomas in vitro. Neuropathol Appl Neurobiol 19: 146–151.
McDermott JR, Gibson AM. 1997. Degradation of Alzheimer's β-amyloid protein by human and rat brain peptidases: Involvement of insulin-degrading enzyme. Neurochem Res 22: 49–56.
McDonald JK. 1985. An overview of protease specificity and catalytic mechanisms: Aspects related to nomenclature and classification. Histochem J 17: 773–785.
McGeer PL, McGeer EG. 2001. Inflammation, autotoxicity, and Alzheimer's disease. Neurobiol Aging 22: 799–809.
McLaurin J, Yang D, Yip CM, Fraser PE. 2000. Review: Modulating factors in amyloid-β fibril formation. J Struct Biol 130: 259–270.
McMahon MJ, Bowen M, Mayer AD, Cooper EH. 1984. Relation of α2-macroglobulin and other antiproteases to the clinical features of acute pancreatitis. Am J Surg 147: 164–170.
Meier R, Spreyer P, Ortmann R, Harel A, Monard D. 1989. Induction of glia-derived nexin after lesion of a peripheral nerve. Nature 342: 548–550.
Meins M, Piosik P, Schaeren-Wiemers N, Franzoni S, Troncoso E, et al. 2001. Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic neurons. J Neurosci 21: 8830–8841.
Melchor JP, Pawlak R, Strickland S. 2003. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-β (Aβ) degradation and inhibits Aβ-induced neurodegeneration. J Neurosci 23: 8867–8871.
Merzeniuk ZA, Churliaev Iu A, Nikiforova NV, Kuksinskii VA, Lykova OF, 2000. The possible role of α2-macroglobulin in regulating the immune components of the brain in tick-borne encephalitis. Zh Mikrobiol Epidemiol Immunobiol 76–78.
Mignatti P, Rifkin DB. 1993. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73: 161–195.
Milward EA, Papadopoulos R, Fuller SJ, Moir RD, Small D, et al. 1992. The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 9: 129–137.
Miranda E, Romisch K, Lomas DA. 2004. Mutants of neuroserpin that cause dementia accumulate as polymers within the endoplasmic reticulum. J Biol Chem 279: 28283–28291.
Miyake T, Gahara Y, Nakayama M, Yamada H, Uwabe K, Kitamura T. 1996. Upregulation of cystatin C by microglia in the rat facial nucleus following axotomy. Brain Res Mol Brain Res 37: 273–282.
Miyazaki K, Hasegawa M, Funahashi K, Umeda M. 1993. A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature 362: 839–841.
Mohanam S, Chintala SK, Mohan PM, Sawaya R, Lagos GK, et al. 1998. Increased invasion of neuroglioma cells transfected with urokinase plasminogen activator receptor cDNA. Int J Oncol 13: 1285–1290.
Mohanam S, Wang SW, Rayford A, Yamamoto M, Sawaya R, et al. 1995. Expression of tissue inhibitors of metalloproteinases: Negative regulators of human glioblastoma invasion in vivo. Clin Exp Metastasis 13: 57–62.
Monard D. 1993. Tinkering with certain blood components can engender distinct functions in the nervous system. Perspect Dev Neurobiol 1: 165–168.
Montgomery AM, Mueller BM, Reisfeld RA, Taylor SM, DeClerck YA. 1994. Effect of tissue inhibitor of the matrix metalloproteinases-2 expression on the growth and spontaneous metastasis of a human melanoma cell line. Cancer Res 54: 5467–5473.
Mook OR, Frederiks WM, Van Noorden CJ. 2004. The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta 1705: 69–89.
Mucke L, Yu GQ, McConlogue L, Rockenstein EM, Abraham CR, et al. 2000. Astroglial expression of human α1-antichymotrypsin enhances Alzheimer-like pathology in amyloid protein precursor transgenic mice. Am J Pathol 157: 2003–2010.
Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, et al. 1992a. A pathogenic mutation for probable Alzheimer's disease in the amyloid precursor protein gene at the N terminus of β-amyloid. Nature Genet 1: 345–347.
Mullan M, Houlden H, Windelspecht M, Fidani L, Lombardi C, et al. 1992b. A locus for familial early-onset Alzheimer's disease on the long arm of chromosome 14, proximal to the α1-antichymotrypsin gene. Nature Genet 2: 340–342.
Munoz E, Obach V, Oliva R, Marti MJ, Ezquerra M, et al. 1999. α1-Antichymotrypsin gene polymorphism and susceptibility to Parkinson's disease. Neurology 52: 297–301.
Murrell J, Farlow M, Ghetti B, Benson MD. 1991. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254: 97–99.
Murrell JR, Spillantini MG, Zolo P, Guazzelli M, Smith MJ, et al. 1999. Tau gene mutation G389R causes a tauopathy with abundant Pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol 58: 1207–1226.
Musil D, Zucic D, Turk D, Engh RA, Mayr I, et al. 1991. The refined 2.15 Å X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J 10: 2321–2330.
Myers A, Wavrant De-Vrieze F, Holmans P, Hamshere M, Crook R, et al. 2002. Full genome screen for Alzheimer's disease: Stage II analysis. Am J Med Genet 114: 235–244.
Nagase H. 1997. Activation mechanisms of matrix metalloproteinases. Biol Chem 378: 151–160.
Nakagawa T, Kubota T, Kabuto M, Fujimoto N, Okada Y. 1996. Secretion of matrix metalloproteinase-2 (72 kDa gelatinase/type IV collagenase = gelatinase A) by malignant human glioma cell lines: Implications for the growth and cellular invasion of the extracellular matrix. J Neurooncol 28: 13–24.
Nakagawa T, Kubota T, Kabuto M, Sato K, Kawano H, et al. 1994. Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. J Neurosurg 81: 69–77.
Nakajima M, Welch DR, Belloni PN, Nicolson GL. 1987. Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47: 4869–4876.
Nakamura Y, Takeda M, Suzuki H, Hattori H, Tada K, et al. 1991. Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease. Neurosci Lett 130: 195–198.
Nakamura Y, Takeda M, Suzuki H, Morita H, Tada K, et al. 1989. Lysosome instability in aged rat brain. Neurosci Lett 97: 215–220.
Nakano A, Tani E, Miyazaki K, Furuyama J, Matsumoto T. 1993. Expressions of matrilysin and stromelysin in human glioma cells. Biochem Biophys Res Commun 192: 999–1003.
Nakano A, Tani E, Miyazaki K, Yamamoto Y, Furuyama J. 1995. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. J Neurosurg 83: 298–307.
Narita M, Holtzman DM, Schwartz AL, Bu G. 1997. α2-macroglobulin complexes with and mediates the endocytosis of β-amyloid peptide via cell surface low-density lipoprotein receptor-related protein. J Neurochem 69: 1904–1911.
Naruse S, Igarashi S, Kobayashi H, Aoki K, Inuzuka T, et al. 1991. Mis-sense mutation Val----Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 337: 978–979.
Neurath H. 1989. The diversity of proteolytic enzymes. Proteolytic enzymes, a practical approach. Beynon RJ, Bond JS, editors. Oxford: Oxford University Press.
Ni J, Abrahamson M, Zhang M, Fernandez MA, Grubb A, et al. 1997. Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins. J Biol Chem 272: 10853–10858.
Nilsson LN, Arendash GW, Leighty RE, Costa DA, Low MA, et al. 2004. Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation. Neurobiol Aging 25: 1153–1167.
Nilsson M, Wang X, Rodziewicz-Motowidlo S, Janowski R, Lindstrom V, et al. 2004. Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C: Use of engineered disulfide bridges, antibodies, and carboxymethylpapain to stabilize the monomeric form of cystatin C. J Biol Chem 279: 24236–24245.
Nishio C, Yoshida K, Nishiyama K, Hatanaka H, Yamada M. 2000. Involvement of cystatin C in oxidative stress-induced apoptosis of cultured rat CNS neurons. Brain Res 873: 252–262.
Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, et al. 1995. Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 15: 1001–1011.
Nomura T, Katunuma N. 2005. Involvement of cathepsins in the invasion, metastasis, and proliferation of cancer cells. J Med Invest 52: 1–9.
Ohyama H, Hosomi N, Takahashi T, Mizushige K, Kohno M. 2001. Thrombin inhibition attenuates neurodegeneration and cerebral edema formation following transient forebrain ischemia. Brain Res 902: 264–271.
Olafsson I, Thorsteinsson L, Jensson O. 1996. The molecular pathology of hereditary cystatin C amyloid angiopathy causing brain hemorrhage. Brain Pathol 6: 121–126.
Olson JM, Goddard KA, Dudek DM. 2002. A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region. Am J Hum Genet 71: 154–161.
Onda M, Belorgey D, Sharp LK, Lomas DA. 2005. Latent S49P neuroserpin forms polymers in the dementia familial encephalopathy with neuroserpin inclusion bodies. J Biol Chem 280: 13735–13741.
Ono Y, Sorimachi H, Suzuki K. 1998. Structure and physiology of calpain, an enigmatic protease. Biochem Biophys Res Commun 245: 289–294.
Oppenheim RW, Prevette D, Haverkamp LJ, Houenou L, Yin QW, et al. 1993. Biological studies of a putative avian muscle-derived neurotrophic factor that prevents naturally occurring motoneuron death in vivo. J Neurobiol 24: 1065–1079.
Osterwalder T, Cinelli P, Baici A, Pennella A, Krueger SR, et al. 1998. The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin. J Biol Chem 273: 2312–2321.
Osterwalder T, Contartese J, Stoeckli ET, Kuhn TB, Sonderegger P. 1996. Neuroserpin, an axonally secreted serine protease inhibitor. EMBO J 15: 2944–2953.
Palm DE, Knuckey NW, Primiano MJ, Spangenberger AG, Johanson CE. 1995. Cystatin C, a protease inhibitor, in degenerating rat hippocampal neurons following transient forebrain ischemia. Brain Res 691: 1–8.
Palsdottir A, Abrahamson M, Thorsteinsson L, Arnason A, Olafsson I, et al. 1988. Mutation in cystatin C gene causes hereditary brain hemorrhage. Lancet 2: 603–604.
Parmar PK, Coates LC, Pearson JF, Hill RM, Birch NP. 2002. Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cells. J Neurochem 82: 1406–1415.
Pennacchio LA, Bouley DM, Higgins KM, Scott MP, Noebels JL, et al. 1998. Progressive ataxia, myoclonic epilepsy, and cerebellar apoptosis in cystatin B-deficient mice. Nat Genet 20: 251–258.
Pennacchio LA, Lehesjoki AE, Stone NE, Willour VL, Virtaneva K, et al. 1996. Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1) (see comments). Science 271: 1731–1734.
Peppard JV, Knap AK. 1999. Effect of the selective and nonselective cysteine protease inhibitors on the intracellular processing of interleukin 6 by HEPG2 cells. In Vitro Cell Dev Biol Anim 35: 459–464.
Peress NS, Perillo E. 1995. Differential expression of TGF-β 1, 2, and 3 isotypes in Alzheimer's disease: a comparative immunohistochemical study with cerebral infarction, aged human, and mouse control brains. J Neuropathol Exp Neurol 54: 802–811.
Perez A, Morelli L, Cresto JC, Castano EM. 2000. Degradation of soluble amyloid β-peptides 1–40, 1–42, and the Dutch variant 1–40Q by insulin-degrading enzyme from Alzheimer disease and control brains. Neurochem Res 25: 247–255.
Pericak-Vance MA, Bass MP, Yamaoka LH, Gaskell PC, Scott WK, et al. 1997. Complete genomic screen in late-onset familial Alzheimer's disease. Evidence for a new locus on chromosome 12. JAMA 278: 1237–1241.
Perry VH, Andersson PB, Gordon S. 1993. Macrophages and inflammation in the central nervous system. Trends Neurosci 16: 268–273.
Ponton A, Coulombe B, Skup D. 1991. Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity. Cancer Res 51: 2138–2143.
Poole AR, Tiltman KJ, Recklies AD, Stoker TA. 1978. Differences in secretion of the proteinase cathepsin B at the edges of human breast carcinomas and fibroadenomas. Nature 273: 545–547.
Potempa J, Korzus E, Travis J. 1994. The serpin superfamily of proteinase inhibitors: Structure, function, and regulation. J Biol Chem 269: 15957–15960.
Price A, Shi Q, Morris D, Wilcox ME, Brasher PM, et al. 1999. Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. Clin Cancer Res 5: 845–854.
Price DL, Sisodia SS. 1998. Mutant genes in familial Alzheimer's disease and transgenic models. Annu Rev Neurosci 21: 479–505.
Qiu WQ, Ferreira A, Miller C, Koo EH, Selkoe DJ. 1995. Cell-surface β-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner. J Neurosci 15: 2157–2167.
Raithatha SA, Muzik H, Rewcastle NB, Johnston RN, Edwards DR, et al. 2000. Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas. Neuro-oncol 2: 145–150.
Ramnath N, Creaven PJ. 2004. Matrix metalloproteinase inhibitors. Curr Oncol Rep 6: 96–102.
Rao JS, Steck PA, Mohanam S, Stetler-Stevenson WG, Liotta LA, et al. 1993. Elevated levels of M r 92,000 type IV collagenase in human brain tumors. Cancer Res 53: 2208–2211.
Rao JS, Yamamoto M, Mohanam S, Gokaslan ZL, Fuller GN, et al. 1996. Expression and localization of 92-kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas. Clin Exp Metastasis 14: 12–18.
Rawlings ND, Barrett AJ. 1990. Evolution of proteins of the cystatin superfamily. J Mol Evol 30: 60–71.
Rebeck GW, Harr SD, Strickland DK, Hyman BT. 1995. Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, the α2-macroglobulin receptor/low-density lipoprotein receptor-related protein. Ann Neurol 37: 211–217.
Reilly CE. 2001. Neprilysin content is reduced in Alzheimer brain areas. J Neurol 248: 159–160.
Rempel SA, Rosenblum ML, Mikkelsen T, Yan PS, Ellis KD, et al. 1994. Cathepsin B expression and localization in glioma progression and invasion. Cancer Res 54: 6027–6031.
Rider BJ, Fraga E, Yu Q, Singh B. 1996. Immune responses to self peptides naturally presented by murine class II major histocompatibility complex molecules. Mol Immunol 33: 625–633.
Rinne R, Saukko P, Jarvinen M, Lehesjoki AE. 2002. Reduced cystatin B activity correlates with enhanced cathepsin activity in progressive myoclonus epilepsy. Ann Med 34: 380–385.
Robakis NK, Ramakrishna N, Wolfe G, Wisniewski HM. 1987. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci USA 84: 4190–4194.
Roberg K, Ollinger K. 1998. Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes. Am J Pathol 152: 1151–1156.
Roberts RM, Mathialagan N, Duffy JY, Smith GW. 1995. Regulation and regulatory role of proteinase inhibitors. Crit Rev Eukaryot Gene Exp 5: 385–436.
Roberts SB, Ripellino JA, Ingalls KM, Robakis NK, Felsenstein KM. 1994. Nonamyloidogenic cleavage of the β-amyloid precursor protein by an integral membrane metalloendopeptidase. J Biol Chem 269: 3111–3116.
Roberts-Lewis JM, Marcy VR, Zhao Y, Vaught JL, Siman R, et al. 1993. Aurintricarboxylic acid protects hippocampal neurons from NMDA- and ischemia-induced toxicity in vivo. J Neurochem 61: 378–381.
Rochefort H, Capony F, Garcia M. 1990. Cathepsin D: a protease involved in breast cancer metastasis. Cancer Metastasis Rev 9: 321–331.
Rogaeva E, Premkumar S, Song Y, Sorbi S, Brindle N, et al. 1998. Evidence for an Alzheimer's disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA 280: 614–618.
Roks G, Cruts M, Slooter AJ, Dermaut B, Hofman A, et al. 2001. The cystatin C polymorphism is not associated with early onset Alzheimer's disease. Neurology 57: 366–367.
Rosa ML, Guimaraes FS, de Oliveira RM, Padovan CM, Pearson RC, et al. 2005. Restraint stress induces β-amyloid precursor protein mRNA expression in the rat basolateral amygdala. Brain Res Bull 65: 69–75.
Rosenblatt DE, Geula C, Mesulam MM. 1989. Protease nexin I immunostaining in Alzheimer's disease. Ann Neurol 26: 628–634.
Rudensky A, Preston-Hurlburt P, Hong SC, Barlow A, Janeway CA Jr. 1991. Sequence analysis of peptides bound to MHC class II molecules. Nature 353: 622–627.
Saido TC, Sorimachi H, Suzuki K. 1994. Calpain: New perspectives in molecular diversity and physiological–pathological involvement. FASEB J 8: 814–822.
Saitoh E, Sabatini LM, Eddy RL, Shows TB, Azen EA, et al. 1989. The human cystatin C gene (CST3) is a member of the cystatin gene family, which is localized on chromosome 20. Biochem Biophys Res Commun 162: 1324–1331.
Saitoh T, Sundsmo M, Roch JM, Kimura N, Cole G, et al. 1989. Secreted form of amyloid-β protein precursor is involved in the growth regulation of fibroblasts. Cell 58: 615–622.
Sakai A, Ujike H, Nakata K, Takehisa Y, Imamura T, et al. 2004. Association of the neprilysin gene with susceptibility to late-onset Alzheimer's disease. Dement Geriatr Cogn Disord 17: 164–169.
Sanchez JC, Guillaume E, Lescuyer P, Allard L, Carrette O, et al. 2004. Cystatin C as a potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt–Jakob disease. Proteomics 4: 2229–2233.
Sastre M, Calero M, Pawlik M, Mathews PM, Kumar A, et al. 2004. Binding of cystatin C to Alzheimer's amyloid b inhibits amyloid fibril formation. Neurobiol Aging 25: 1033–1043.
Saunders AJ, Bertram L, Mullin K, Sampson AJ, Latifzai K, et al. 2003. Genetic association of Alzheimer's disease with multiple polymorphisms in α2-macroglobulin. Hum Mol Genet 12: 2765–2776.
Saunders AJ, Tanzi, RE. 2003. Welcome to the complex disease world: α2-Macroglobulin and Alzheimer's disease. Exp Neurol 184: 50–53.
Sawaya RE, Yamamoto M, Gokaslan ZL, Wang SW, Mohanam S, et al. 1996. Expression and localization of 72-kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. Clin Exp Metastasis 14: 35–42.
Schorr EE, Arnason BG, Astrom KE, Darzynkiewicz Z. 1978. Treatment of mouse muscular dystrophy with the protease inhibitor pepstatin. J Neuropathol Exp Neurol 37: 263–268.
Schremmer-Danninger E, Naidoo S, Neuhof C, Valeske K, Snyman C, et al. 2004. Visualization of tissue kallikrein, kininogen, and kinin receptors in human skin following trauma and in dermal diseases. Biol Chem 385: 1069–1076.
Schubert D. 1997. Serpins inhibit the toxicity of amyloid peptides. Eur J Neurosci 9: 770–777.
Schubert D, Behl C. 1993. The expression of amyloid-β protein precursor protects nerve cells from β-amyloid and glutamate toxicity and alters their interaction with the extracellular matrix. Brain Res 629: 275–282.
Schultz RM, Silberman S, Persky B, Bajkowski AS, Carmichael DF. 1988. Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion invasion and lung colonization by murine B16-F10 melanoma cells. Cancer Res 48: 5539–5545.
Scott WK, Grubber JM, Abou-Donia SM, Church TD, Saunders AM, et al. 1999. Further evidence linking late-onset Alzheimer's disease with chromosome 12. JAMA 281: 513–514.
Scott WK, Grubber JM, Conneally PM, Small GW, Hulette CM, et al. 2000. Fine mapping of the chromosome 12 late-onset Alzheimer disease locus: Potential genetic and phenotypic heterogeneity. Am J Hum Genet 66: 922–932.
Seeds NW, Williams BL, Bickford PC. 1995. Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning. Science 270: 1992–1994.
Seelmeier S, Schmidt H, Turk V, Helm von der K. 1988. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci USA 85: 6612–6616.
Shannon P, Pennacchio LA, Houseweart MK, Minassian BA, Myers RM. 2002. Neuropathological changes in a mouse model of progressive myoclonus epilepsy: Cystatin B deficiency and Unverricht–Lundborg disease. J Neuropathol Exp Neurol 61: 1085–1091.
Shea TB. 1995. Role of glial-derived nexin in neuronal differentiation and in acute brain injury and potential involvement in exacerbation of neurodegeneration in Alzheimer's disease. Brain Res Brain Res Rev 20: 171–184.
Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, et al. 1995. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375: 754–760.
Shibata M, Yamada S, Kumar SR, Calero M, Bading J, et al. 2000. Clearance of Alzheimer's amyloid-ss(1–40) peptide from brain by LDL receptor-related protein-1 at the blood–brain barrier. J Clin Invest 106: 1489–1499.
Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, et al. 2001. Ubiquitination of a new form of α-synuclein by parkin from human brain: Implications for Parkinson's disease. Science 293: 263–269.
Shridhar R, Zhang J, Song J, Booth BA, Kevil CG, et al. 2004. Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells. Oncogene 23: 2206–2215.
Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, et al. 2001. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 276: 33293–33296.
Simmen RC, Michel FJ, Fliss AE, Smith LC, Fliss MF. 1992. Ontogeny, immunocytochemical localization, and biochemical properties of the pregnancy-associated uterine elastase/cathepsin-G protease inhibitor, antileukoproteinase (ALP): Monospecific antibodies to a synthetic peptide recognize native ALP. Endocrinology 130: 1957–1965.
Siren V, Antinheimo JP, Jaaskelainen J, Bohling T, Carpen O, et al. 2004. Plasminogen activation in neurofibromatosis 2-associated and sporadic schwannomas. Acta Neurochir (Wien) 146: 111–118.
Sivaparvathi M, McCutcheon I, Sawaya R, Nicolson GL, Rao JS. 1996a. Expression of cysteine protease inhibitors in human gliomas and meningiomas. Clin Exp Metastasis 14: 344–350.
Sivaparvathi M, Sawaya R, Chintala SK, Go Y, Gokaslan ZL, et al. 1996b. Expression of cathepsin D during the progression of human gliomas. Neurosci Lett 208: 171–174.
Sivaparvathi M, Sawaya R, Gokaslan ZL, Chintala SK, Rao JS. 1996c. Expression and the role of cathepsin H in human glioma progression and invasion. Cancer Lett 104: 121–126.
Sivaparvathi M, Sawaya R, Wang SW, Rayford A, Yamamoto M, et al. 1995. Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis 13: 49–56.
Sivaparvathi M, Yamamoto M, Nicolson GL, Gokaslan ZL, Fuller GN, et al. 1996d. Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas. Clin Exp Metastasis 14: 27–34.
Sloane BF, Rozhin J, Johnson K, Taylor H, Crissman JD, et al. 1986. Cathepsin B: association with plasma membrane in metastatic tumors. Proc Natl Acad Sci USA 83: 2483–2487.
Small DH, Nurcombe V, Reed G, Clarris H, Moir R, et al. 1994. A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci 14: 2117–2127.
Smith-Swintosky VL, Zimmer S, Fenton JW, 2nd and Mattson MP. 1995. Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury. J Neurosci 15: 5840–5850.
Soeda S, Imatoh T, Ochiai T, Koyanagi S, Shimeno H. 2004. Plasminogen activator inhibitor-1 aids survival of neurites on neurons derived from pheochromocytoma (PC-12) cells. Neuroreport 15: 855–858.
Sohar I, Laszlo A, Gaal K, Mechler F. 1988. Cysteine and metalloproteinase activities in serum of Duchenne muscular dystrophic genotypes. Biol Chem Hoppe Seyler. 369 Suppl: 277–279.
Sorimachi H, Ishiura S, Suzuki K. 1997. Structure and physiological function of calpains. Biochem J. 328 (Pt 3): 721–732.
Sorimachi H, Saido TC, Suzuki K. 1994. New era of calpain research. Discovery of tissue-specific calpains. FEBS Lett 343: 1–5.
Sotiropoulou G, Anisowicz A, Sager R. 1997. Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, downregulated in breast cancer. J Biol Chem 272: 903–910.
Sottrup-Jensen L. 1989. α-Macroglobulins: Structure, shape, and mechanism of proteinase complex formation. J Biol Chem 264: 11539–11542.
Sottrup-Jensen L, Borth W, Hall M, Quigley JP, Armstrong PB. 1990. Sequence similarity between α2-macroglobulin from the horseshoe crab, Limulus polyphemus, and proteins of the α2-macroglobulin family from mammals. Comp Biochem Physiol B 96: 621–625.
Starkey PM, Barrett AJ. 1982. Evolution of α2-macroglobulin. The demonstration in a variety of vertebrate species of a protein resembling human α2-macroglobulin. Biochem J 205: 91–95.
Stein PE, Tewkesbury DA, Carrell RW. 1989. Ovalbumin and angiotensinogen lack serpin S-R conformational change. Biochem J 262: 103–107.
Steinhoff T, Moritz E, Wollmer MA, Mohajeri MH, Kins S, et al. 2001. Increased cystatin c in astrocytes of transgenic mice expressing the K670N-M671L mutation of the amyloid precursor protein and deposition in brain amyloid plaques. Neurobiol Dis 8: 647–654.
Stenman G, Astrom AK, Roijer E, Sotiropoulou G, Zhang M, et al. 1997. Assignment of a novel cysteine proteinase inhibitor (CST6) to 11q13 by fluorescence in situ hybridization. Cytogenet Cell Genet 76: 45–46.
Stetler G, Brewer MT, Thompson RC. 1986. Isolation and sequence of a human gene encoding a potent inhibitor of leukocyte proteases. Nucleic Acids Res 14: 7883–7896.
Stormorken H, Briseid K, Hellum B, Hoem NO, Johansen HT, et al. 1990. A new case of total kininogen deficiency. Thromb Res 60: 457–467.
Strauss S, Bauer J, Ganter U, Jonas U, Berger M, et al. 1992. Detection of interleukin-6 and α2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients. Lab Invest 66: 223–230.
Striggow F, Riek M, Breder J, Henrich-Noack P, Reymann KG, et al. 2000. The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations. Proc Natl Acad Sci USA 97: 2264–2269.
Strojnik T, Kos J, Zidanik B, Golouh R, Lah T. 1999. Cathepsin B immunohistochemical staining in tumor and endothelial cells is a new prognostic factor for survival in patients with brain tumors. Clin Cancer Res 5: 559–567.
Sun H, Li N, Wang X, Liu S, Chen T, et al. 2003. Molecular cloning and characterization of a novel cystatin-like molecule, CLM, from human bone marrow stromal cells. Biochem Biophys Res Commun 301: 176–182.
Sun Q. 1989. Growth stimulation of 3T3 fibroblasts by cystatin. Exp Cell Res 180: 150–160.
Suzuki K, Sorimachi H, Yoshizawa T, Kinbara K, Ishiura S. 1995. Calpain: Novel family members, activation, and physiologic function. Biol Chem Hoppe Seyler 376: 523–529.
Suzuki N, Cheung TT, Cai XD, Odaka A, Otvos L Jr, et al. 1994. An increased percentage of long amyloid-β protein secreted by familial amyloid-β protein precursor (βAPP717) mutants. Science 264: 1336–1340.
Takao M, Benson MD, Murrell JR, Yazaki M, Piccardo P, et al. 2000. Neuroserpin mutation S52R causes neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy. J Neuropathol Exp Neurol 59: 1070–1086.
Tamaoka A, Odaka A, Ishibashi Y, Usami M, Sahara N, et al. 1994. APP717 missense mutation affects the ratio of amyloid β protein species (Aβ1–42/43 and Aβ1–40) in familial Alzheimer's disease brain. J Biol Chem 269: 32721–32724.
Tandon AK, Clark GM, Chamness GC, Chirgwin JM, McGuire WL. 1990. Cathepsin D and prognosis in breast cancer. N Engl J Med 322: 297–302.
Tang G, Xie H, Xu L, Hao Y, Lin D, et al. 2002. Genetic study of apolipoprotein E gene, α-1 antichymotrypsin gene in sporadic Parkinson's disease. Am J Med Genet 114: 446–449.
Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, et al. 1987. Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235: 880–884.
Taupin P, Ray J, Fischer WH, Suhr ST, Hakansson K, et al. 2000. FGF-2-Responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 28: 385–397.
Tavera C, Leung-Tack J, Prevot D, Gensac MC, Martinez J, et al. 1992. Cystatin C secretion by rat glomerular mesangial cells: Autocrine loop for in vitro growth-promoting activity. Biochem Biophys Res Commun 182: 1082–1088.
Teesalu T, Kulla A, Simisker A, Siren V, Lawrence DA, et al. 2004. Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system. Thromb Haemost 92: 358–368.
Thiesse M, Millar SJ, Dickinson DP. 1994. The human type-2 cystatin gene family consists of eight to nine members, with at least seven genes clustered at a single locus on human chromosome 20. DNA Cell Biol 13: 97–116.
Thomas DJ, Richards AD, Kay J. 1989. Inhibition of aspartic proteinases by α2-macroglobulin. Biochem J 259: 905–907.
Thompson RC, Ohlsson K. 1986. Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proc Natl Acad Sci USA 83: 6692–6696.
Thomssen C, Schmitt M, Goretzki L, Oppelt P, Pache L, et al. 1995. Prognostic value of the cysteine proteases cathepsins B and cathepsin L in human breast cancer. Clin Cancer Res 1: 741–746.
Thorgeirsson UP, Liotta LA, Kalebic T, Margulies IM, Thomas K, et al. 1982. Effect of natural protease inhibitors and a chemoattractant on tumor cell invasion in vitro. J Natl Cancer Inst 69: 1049–1054.
Tooyama I, Kawamata T, Akiyama H, Moestrup SK, Gliemann J, et al. 1993. Immunohistochemical study of α2-macroglobulin receptor in Alzheimer and control postmortem human brain. Mol Chem Neuropathol 18: 153–160.
Trabandt A, Gay RE, Fassbender HG, Gay S. 1991. Cathepsin B in synovial cells at the site of joint destruction in rheumatoid arthritis. Arthritis Rheum 34: 1444–1451.
Tran PB, Miller RJ. 1999. Aggregates in neurodegenerative disease: Crowds and power? Trends Neurosci 22: 194–197.
Travis J, Salvesen GS. 1983. Human plasma proteinase inhibitors. Annu Rev Biochem 52: 655–709.
Tsirka SE, Rogove AD, Strickland S. 1996. Neuronal cell death and tPA. Nature 384: 123–124.
Tsuchiya K, Kohda Y, Yoshida M, Zhao L, Ueno T, et al. 1999. Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors. Exp Neurol 155: 187–194.
Tsuobi R, Kurita Y, Negi M, Ogawa H. 1985. A specific inhibitor of keratinolytic proteinase from Candida albicans could inhibit the cell growth of C. albicans. J Invest Dermatol 85: 438–440.
Tumminello FM, Bernacki RJ, Gebbia N, Leto G. 1993. Pepstatins: Aspartic proteinase inhibitors having potential therapeutic applications. Med Res Rev 13: 199–208.
Turk B, Krizaj I, Kralj B, Dolenc I, Popovic T, et al. 1993. Bovine stefin C, a new member of the stefin family. J Biol Chem 268: 7323–7329.
Turk B, Turk D, Turk V. 2000. Lysosomal cysteine proteases: more than scavengers. Biochim Biophys Acta 1477: 98–111.
Turk B, Turk V, Turk D. 1997. Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol Chem 378: 141–150.
Turk V, Bode W. 1991. The cystatins: Protein inhibitors of cysteine proteinases. FEBS Lett 285: 213–219.
Turk V, Kos J, Gurncar G, Tabira B. 2001. Lysosomal cysteine proteases and their protein inhibitors. Role of proteases in the pathophysiology of neurodegenerative diseases. Lajtha A, Banik N, editors. New York: Kluwer Academic/Plenum Publishers; 227–240.
Turner AJ, Tanzawa K. 1997. Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. FASEB J 11: 355–364.
Twining SS. 1994. Regulation of proteolytic activity in tissues. Crit Rev Biochem Mol Biol 29: 315–383.
Umezawa H. 1982. Low-molecular weight enzyme inhibitors of microbial origin. Annu Rev Microbiol 36: 75–99.
Umezawa H, Aoyagi T, Morishima H, Kunimoto S, Matsuzaki M. 1970. Chymostatin, a new chymotrypsin inhibitor produced by actinomycetes. J Antibiot (Tokyo) 23: 425–427.
van Gent D, Sharp P, Morgan K, Kalsheker N. 2003. Serpins: Structure, function, and molecular evolution. Int J Biochem Cell Biol 35: 1536–1547.
Van Gool D, De Strooper B, Van Leuven F, Triau E, Dom R. 1993. α2-Macroglobulin expression in neuritic-type plaques in patients with Alzheimer's disease. Neurobiol Aging 14: 233–237.
Vaughan PJ, Su J, Cotman CW, Cunningham DD. 1994. Protease nexin-1, a potent thrombin inhibitor, is reduced around cerebral blood vessels in Alzheimer's disease. Brain Res 668: 160–170.
Velasco F, Torres A, Guerrero A, Andres P, Guerrero R, et al. 1986. Behaviour of the contact phase of blood coagulation in the adult respiratory distress syndrome (ARDS). Thromb Haemost 55: 357–360.
Vinters HV, Nishimura GS, Secor DL, Pardridge WM. 1990. Immunoreactive A4 and γ-trace peptide colocalization in amyloidotic arteriolar lesions in brains of patients with Alzheimer's disease. Am J Pathol 137: 233–240.
Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, et al. 1998. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93: 411–422.
Wagner SL, Geddes JW, Cotman CW, Lau AL, Gurwitz D, et al. 1989. Protease nexin-1, an antithrombin with neurite outgrowth activity, is reduced in Alzheimer disease. Proc Natl Acad Sci USA 86: 8284–8288.
Wakasugi K, Nakano T, Morishima I. 2004. Association of human neuroglobin with cystatin C, a cysteine proteinase inhibitor. Biochemistry 43: 5119–5125.
Walker LC, Le Vine H, 3rd. 2000. The cerebral proteopathies. Neurobiol Aging 21: 559–561.
Wallace W, Ahlers ST, Gotlib J, Bragin V, Sugar J, et al. 1993. Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. Proc Natl Acad Sci USA 90: 8712–8716.
Wallace WC, Akar CA, Lyons WE, Kole HK, Egan JM, et al. 1997. Amyloid precursor protein requires the insulin-signaling pathway for neurotrophic activity. Brain Res Mol Brain Res 52: 213–227.
Wallace WC, Lieberburg I, Schenk D, Vigo-Pelfrey C, Davis KL, et al. 1995. Chronic elevation of secreted amyloid precursor protein in subcortically lesioned rats, and its exacerbation in aged rats. J Neurosci 15: 4896–4905.
Wang X, DeKosky ST, Luedecking-Zimmer E, Ganguli M, Kamboh IM. 2002. Genetic variation in α1-antichymotrypsin and its association with Alzheimer's disease. Hum Genet 110: 356–365.
Wang YC, Liu HC, Liu TY, Hong CJ, Tsai SJ. 2001. Genetic association analysis of α1-antichymotrypsin polymorphism in Parkinson's disease. Eur Neurol 45: 254–256.
Wang Z, Wu D, Vinters HV. 2002. Hypoxia and reoxygenation of brain microvascular smooth muscle cells in vitro: Cellular responses and expression of cerebral amyloid angiopathy-associated proteins. APMIS 110: 423–434.
Warfel AH, Zucker-Franklin D, Frangione B, Ghiso J. 1987. Constitutive secretion of cystatin C (γ-trace) by monocytes and macrophages and its downregulation after stimulation. J Exp Med 166: 1912–1917.
Webster S, Rogers J. 1996. Relative efficacies of amyloid-β peptide (Aβ) binding proteins in Aβ aggregation. J Neurosci Res 46: 58–66.
Wei L, Berman Y, Castano EM, Cadene M, Beavis RC, et al. 1998. Instability of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type. J Biol Chem 273: 11806–11814.
Wei L, Walker LC, Levy E. 1996. Cystatin C: Icelandic-like mutation in an animal model of cerebrovascular β amyloidosis. Stroke 27: 2080–2085.
Wildenthal K. 1978. Lysosomal alterations in ischemic myocardium: Result or cause of myocellular damage? J Mol Cell Cardiol 10: 595–603.
Wisniewski KE, Wisniewski HM, Wen GY. 1985. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol 17: 278–282.
Woessner JF Jr. 1991. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5: 2145–2154.
Wu WS, Holmans P, Wavrant-De Vrieze F, Shears S, Kehoe P, et al. 1998. Genetic studies on chromosome 12 in late-onset Alzheimer's disease. JAMA 280: 619–622.
Xia W, Ostaszewski BL, Kimberly WT, Rahmati T, Moore CL, et al. 2000. FAD mutations in presenilin-1 or amyloid precursor protein decrease the efficacy of a γ-secretase inhibitor: Evidence for direct involvement of PS1 in the γ-secretase cleavage complex. Neurobiol Dis 7: 673–681.
Xiang Y, Nie DS, Lu GX. 2004. Cloning of a novel gene, Cymg1, related to family 2 cystatins and expressed at specific stages of mouse testis development. J Genet 83: 257–263.
Xiang Y, Nie DS, Wang J, Tan XJ, Deng Y, et al. 2005. Cloning, characterization, and primary function study of a novel gene, Cymg1, related to family 2 cystatins. Acta Biochim Biophys Sin (Shanghai) 37: 11–18.
Xu L, Sheng J, Tang Z, Wu X, Yu Y, et al. 2005. Cystatin C prevents degeneration of rat nigral dopaminergic neurons: In vitro and in vivo studies. Neurobiol Dis 18: 152–165.
Yamada M. 2004. Cerebral amyloid angiopathy and gene polymorphisms. J Neurol Sci 226: 41–44.
Yamada M, Sodeyama N, Itoh Y, Suematsu N, Otomo E, et al. 1998. Association of α1-antichymotrypsin polymorphism with cerebral amyloid angiopathy. Ann Neurol 44: 129–131.
Yamada M, Sodeyama N, Itoh Y, Suematsu N, Otomo E, et al. 1999. A deletion polymorphism of α2-macroglobulin gene and cerebral amyloid angiopathy. Stroke 30: 2277–2279.
Yamamoto M, Kondo I, Ogawa N, Asanuma M, Yamashita Y, et al. 1997. Genetic association between susceptibility to Parkinson's disease and α1-antichymotrypsin polymorphism. Brain Res 759: 153–155.
Yamamoto M, Mohanam S, Sawaya R, Fuller GN, Seiki M, et al. 1996. Differential expression of membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivo and in vitro. Cancer Res 56: 384–392.
Yamashima T, Kohda Y, Tsuchiya K, Ueno T, Yamashita J, et al. 1998. Inhibition of ischemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on “calpain-cathepsin hypothesis”. Eur J Neurosci 10: 1723–1733.
Yamin R, Malgeri EG, Sloane JA, McGraw WT, Abraham CR. 1999. Metalloendopeptidase EC 3.4.24.15 is necessary for Alzheimer's amyloid-β peptide degradation. J Biol Chem 274: 18777–18784.
Yasojima K, Akiyama H, McGeer EG, McGeer PL. 2001. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of β-amyloid peptide. Neurosci Lett 297: 97–100.
Yazaki M, Liepnieks JJ, Murrell JR, Takao M, Guenther B, et al. 2001. Biochemical characterization of a neuroserpin variant associated with hereditary dementia. Am J Pathol 158: 227–233.
Yepes M, Lawrence DA. 2004. Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. Thromb Haemost 91: 457–464.
Yepes M, Sandkvist M, Coleman TA, Moore E, Wu JY, et al. 2002. Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent. J Clin Invest 109: 1571–1578.
Yepes M, Sandkvist M, Wong MK, Coleman TA, Smith E, et al. 2000. Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis. Blood 96: 569–576.
Ying GX, Huang C, Jiang ZH, Liu X, Jing NH, et al. 2002. Upregulation of cystatin C expression in the murine hippocampus following perforant path transections. Neuroscience 112: 289–298.
Yoshioka K, Miki T, Katsuya T, Ogihara T, Sakaki Y. 1991. The 717Val→Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. Biochem Biophys Res Commun 178: 1141–1146.
Younkin SG. 1994. The amyloid-β protein precursor mutations linked to familial Alzheimer's disease alter processing in a way that fosters amyloid deposition. Tohoku J Exp Med 174: 217–223.
Zeeuwen PL, van Vlijmen-Willems IM, Egami H, Schalkwijk J. 2002. Cystatin M/E expression in inflammatory and neoplastic skin disorders. Br J Dermatol 147: 87–94.
Zhang J, Shridhar R, Dai Q, Song J, Barlow SC, et al. 2004. Cystatin m: a novel candidate tumor suppressor gene for breast cancer. Cancer Res 64: 6957–6964.
Zhang L, Song L, Terracina G, Liu Y, Pramanik B, et al. 2001. Biochemical characterization of the γ-secretase activity that produces β-amyloid peptides. Biochemistry 40: 5049–5055.
Zhang R, Tremblay TL, McDermid A, Thibault P, Stanimirovic D. 2003. Identification of differentially expressed proteins in human glioblastoma cell lines and tumors. Glia 42: 194–208.
Zhao G, Reynolds JN, Flavin MP. 2003. Temporal profile of tissue plasminogen activator (tPA) and inhibitor expression after transient focal cerebral ischemia. Neuroreport 14: 1689–1692.
Zucker S, Vacirca J. 2004. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev 23: 101–117.
Zucker-Franklin D, Warfel A, Grusky G, Frangione B, Teitel D. 1987. Novel monocyte-like properties of microglial/astroglial cells. Constitutive secretion of lysozyme and cystatin-C. Lab Invest 57: 176–185.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer Science+Business Media, LLC
About this entry
Cite this entry
Tizon, B., Levy, E. (2007). Protease Inhibitors and their Involvement in Neurological Disorders. In: Lajtha, A., Banik, N. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30379-6_20
Download citation
DOI: https://doi.org/10.1007/978-0-387-30379-6_20
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-30346-8
Online ISBN: 978-0-387-30379-6
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences