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Mechanisms of Aβ clearance and catabolism

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Abstract

Mutations that result in an increased generation of amyloid beta peptide (Aβ) account for less than 5% of Alzheimer’s disease (AD). Data suggesting that late onset AD risk factors play a role in Aβ turnover in the brain have shifted some of the research focus to the study of Aβ clearance and degradation and the impact of these processes on the etiology of Alzheimer’s disease (AD). This review will examine the data obtained from studies performed in knockout and transgenic mice on the proteases; the cells and the physiological mechanisms that play a part in the removal of Aβ from the brain.

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References

  • Abraham R., Myers A., Wavrant-DeVrieze F., et al. (2001) Substantial linkage disequilibrium across the insulin-degrading enzyme locus but no association with late-onset Alzheimer’s disease. Hum. Genet. 109, 642–652.

    Article  CAS  Google Scholar 

  • Ait-Ghezala G., Abdullah L., Crescentini R., et al. (2002) Confirmation of association between D10S583 and Alzheimer’s disease in a case—control sample. Neurosci. Lett. 325, 87–90.

    Article  PubMed  CAS  Google Scholar 

  • Akiyama H., Barger S., Barnum S., et al. (2000) Inflammation and Alzheimer’s disease. Neurobiol. Aging 21, 383–421.

    Article  PubMed  CAS  Google Scholar 

  • Akiyama H., Kondo H., Ikeda K., Kato M., and McGeer P.L. (2001) Immunohistochemical localization of neprilysin in the human cerebral cortex: inverse association with vulnerability to amyloid beta-protein (Abeta) deposition. Brain Res. 902, 277–281.

    Article  PubMed  CAS  Google Scholar 

  • Apelt J., Ach K., and Schliebs R. (2003) Aging-related down-regulation of neprilysin, a putative beta-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of beta-amyloid plaques. Neurosci Lett. 339, 183–186.

    Article  PubMed  CAS  Google Scholar 

  • Authier F., Cameron P. H., and Taupin V. (1996) Association of insulin-degrading enzyme with a 70 kDa cytosolic protein in hepatoma cells. Biochem. J. 319, 149–158.

    PubMed  CAS  Google Scholar 

  • Authier F., Metioui M., Fabrega S., Kouach M., and Briand, G. (2002) Endosomal proteolysis of internalized insulin at the C-terminal region of the B chain by cathepsin D. J. Biol. Chem. 277, 9437–9446.

    Article  PubMed  CAS  Google Scholar 

  • Authier F., Rachubinski R. A., Posner B. I., and Bergeron J. J. (1994) Endosomal proteolysis of insulin by an acidic thiol metalloprotease unrelated to insulin degrading enzyme. J. Biol. Chem. 269, 3010–3016.

    PubMed  CAS  Google Scholar 

  • Bard F., Cannon C., Barbour R., et al. (2000) Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med. 6, 916–919.

    Article  PubMed  CAS  Google Scholar 

  • Barnes K., Doherty S., and Turner A. J. (1995) Endopeptidase-24.11 is the integral membrane peptidase initiating degradation of somatostatin in the hippocampus. J. Neurochem. 64, 1826–1832.

    Article  PubMed  CAS  Google Scholar 

  • Baumeister H., Muller D., Rehbein M., and Richter D. (1993) The rat insulin-degrading enzyme. Molecular cloning and characterization of tissue-specific transcripts. FEBS Lett. 317, 250–254.

    Article  PubMed  CAS  Google Scholar 

  • Bennett R. G., Duckworth W. C., and Hamel F. G. (2000) Degradation of amylin by insulin-degrading enzyme. J. Biol. Chem. 275, 36621–36625.

    Article  PubMed  CAS  Google Scholar 

  • Bernstein H. G., Ansorge S., Riederer P., Reiser M., Frolich L., and Bogerts B. (1999) Insulin-degrading enzyme in the Alzheimer’s disease brain: prominent localization in neurons and senile plaques. Neurosci. Lett. 263, 161–164.

    Article  PubMed  CAS  Google Scholar 

  • Bertram L., Blacker D., Mullin K., et al. (2000) Evidence for genetic linkage of Alzheimer’s disease to chromosome 10q. Science 290, 2302–2303.

    Article  PubMed  CAS  Google Scholar 

  • Bertram L., Saunders A. J., Mullin K., et al. (2002) Further assessment of novel Alzheimer’s disease loci on chromosome 10 and 9. Neurobiol. Aging 23, S324.

    Google Scholar 

  • Blacker D., Wilcox M. A., Laird N. M., et al. (1998) Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat. Genet. 19, 357–360.

    Article  PubMed  CAS  Google Scholar 

  • Boussaha, M., Hannequin, D. Verpillat, P., Brice, A., Frebourg, T., and Campion, D. (2002) Polymorphisms of insulin degrading enzyme gene are not associated with Alzheimer’s disease. Neurosci. Lett. 329, 121–123.

    Article  PubMed  CAS  Google Scholar 

  • Butterfield D. A. and Kanski J. (2002) Methionine residue 35 is critical for the oxidative stress and neurotoxic properties of Alzheimer’s amyloid beta-peptide 1-42. Peptides 23, 1299–1309.

    Article  PubMed  CAS  Google Scholar 

  • Carpentier M., Robitaille Y., DesGroseillers L., Boileau G., and Marcinkiewicz M. (2002) Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy. J. Neuropathol. Exp. Neurol. 61, 849–856.

    PubMed  CAS  Google Scholar 

  • Carson J. A. and Turner A. J. (2002) Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases? J. Neurochem. 81, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Chesneau V., Vekrellis K., Rosner M. R., and Selkoe D. J. (2000) Purified recombinant insulin-degrading enzyme degrades amyloid beta-protein but does not promote its oligomerization. Biochem. J. 351, 509–516.

    Article  PubMed  CAS  Google Scholar 

  • Chui D. H., Tanahashi H., Ozawa K., et al. (1999) Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat. Med. 5, 560–564.

    Article  PubMed  CAS  Google Scholar 

  • Cook D. G., Leverenz J. B., McMillan P. J., et al. (2003) Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer’s disease is associated with the apolipoprotein E-epsilon4 allele. Am. J. Pathol. 162, 313–319.

    PubMed  CAS  Google Scholar 

  • Craft S., Peskind E., Schwartz M. W., Schellenberg G. D., Raskind M., and Porte D., Jr. (1998) Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 50, 164–168.

    PubMed  CAS  Google Scholar 

  • Das P., Murphy M. P., Younkin L. H., Younkin S. G., and Golde T.E. (2001) Reduced effectiveness of Abeta1–42 immunization in APP transgenic mice with significant amyloid deposition. Neurobiol. Aging 22, 721–727.

    Article  PubMed  CAS  Google Scholar 

  • DeMattos R. B., Bales K. R., Cummins D. J., Dodart J. C., Paul S. M., and Holtzman D. M. (2001) Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 98, 8850–8855.

    Article  PubMed  CAS  Google Scholar 

  • DeMattos R. B., Bales K. R., Cummins D. J., Paul S. M., and Holtzman, D. M. (2002) Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer’s disease. Science 295, 2264–2267.

    Article  PubMed  CAS  Google Scholar 

  • DeMattos R. B., Bales K. R., Paul S. M., and Holtzman D. M. (2003) Potential role of endogenous and exogenous Aβ binding molecules in Aβ clearance and metabolism. In Metabolic regulation of amyloid protein and Alzheimer’s disease. Saido T.C. (ed). Landes Bioscience.

  • Duckworth W. C., Bennett R. G., and Hamel F.G. (1998) Insulin degradation: progress and potential. Endocr. Rev. 19, 608–624.

    Article  PubMed  CAS  Google Scholar 

  • Eckman E. A., Reed D. K., and Eckman C. B. (2001) Degradation of the Alzheimer’s amyloid beta peptide by endothelin-converting enzyme. J. Biol. Chem. 276, 24540–24548.

    Article  PubMed  CAS  Google Scholar 

  • Eckman E. A., Watson M., Marlow L., Sambamurti K., and Eckman C. B. (2003) Alzheimer’s disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J. Biol. Chem. 278, 2081–2084.

    Article  PubMed  CAS  Google Scholar 

  • Edbauer D., Willem M., Lammich S., Steiner H., and Haass C. (2002) Insulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD). J. Biol. Chem. 277, 13389–13393.

    Article  PubMed  CAS  Google Scholar 

  • Edland S. D., Wavrant-DeVrieze F., Compton D., et al. (2003) Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer’s disease: evidence of effect modification by ApoE. Neurosci. Lett. 345, 21–24.

    Article  PubMed  CAS  Google Scholar 

  • Emoto N. and Yanagisawa M. (1995) Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum. J. Biol. Chem. 270, 15262–15268.

    Article  PubMed  CAS  Google Scholar 

  • Ertekin-Taner N., Graff-Radford N., Younkin L. H., et al. (2000) Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer’s disease pedigrees. Science 290, 2303–2304.

    Article  PubMed  CAS  Google Scholar 

  • Facchinetti P., Rose C., Scwartz J. C., and Ouimet T. (2003) Ontogeny, regional and cellular distribution of the novel mettalloprotease neprilysin 2 in the rat: A comparison with neprilysin and endothelin-converting enzyme-1. Neuroscience 118, 627–639.

    Article  PubMed  CAS  Google Scholar 

  • Fagan J. M. and Waxman L. (1991) Purification of a protease in red blood cells that degrades oxidatively damaged haemoglobin. Biochem. J. 277, 779–786.

    PubMed  CAS  Google Scholar 

  • Farris W., Mansourian S., Chang Y., et al. (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA 100, 4162–4167.

    Article  PubMed  CAS  Google Scholar 

  • Feuk L., Prince J., Graziano C., Blennow K., and Brookes A. J. (2002) Multiple genes may be involved in explaining the linkage peak on chromosome 10: Evidence from SNP-based association studies. Neurobiol. Aging 23, S424.

    Google Scholar 

  • Frolich L., Blum-Degen D., Bernstein H. G., et al. (1998) Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. J. Neural. Transm. 105, 423–438.

    Article  PubMed  CAS  Google Scholar 

  • Fukami S., Watanabe K., Iwata N., et al. (2002) Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology. Neurosci. Res. 43, 39–56.

    Article  PubMed  CAS  Google Scholar 

  • Hamel F. G., Bennett R. G., Upward J. L., and Duckworth W. C. (2001) Insulin inhibits peroxisomal fatty acid oxidation in isolated rat hepatocytes. Endocrinology 142, 2702–2706.

    Article  PubMed  CAS  Google Scholar 

  • Hamel F. G., Mahoney M. J., and Duckworth W. C. (1991) Degradation of intraendosomal insulin by insulin-degrading enzyme without acidification. Diabetes 40, 436–443.

    Article  PubMed  CAS  Google Scholar 

  • Hamel F. G., Siford G. L., Jones J., and Duckworth W. C. (1997) Intraendosomal degradation of transforming growth factor alpha. Mol. Cell. Endocrinol. 126, 185–192.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman D. M. (2001) Role of apoe/Abeta interactions in the pathogenesis of Alzheimer’s disease and cerebral amyloid angiopathy. J. Mol. Neurosci. 17, 147–155.

    Article  PubMed  CAS  Google Scholar 

  • Howell S., Nalbantoglu J., and Crine P. (1995) Neutral endopeptidase can hydrolyze β-amyloid(1–40) but shows no effect on β-amyloid precursor protein metabolism. Peptides 16, 647–652.

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S. (1998). Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J. Neural. Transm. 105, 415–422.

    Article  PubMed  CAS  Google Scholar 

  • Iwata N., Takaki Y., Fukami S., Tsubuki S., and Saido T. C. (2002) Region-specific reduction of A beta-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging. J. Neurosci. Res. 70, 493–500.

    Article  PubMed  CAS  Google Scholar 

  • Iwata N., Tsubuki S., Takaki Y., et al. (2001) Metabolic regulation of brain Abeta by neprilysin. Science 292, 1550–1552.

    Article  PubMed  CAS  Google Scholar 

  • Iwata N., Tsubuki S., Takaki Y., et al. (2000) Identification of the major Abeta1–42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat. Med. 6, 143–150.

    Article  PubMed  CAS  Google Scholar 

  • Ji Y., Permanne B., Sigurdsson E. M., Holtzman D. M., and Wisniewski T. (2001) Amyloid beta40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice. J. Alzheimers Dis. 3, 23–30.

    PubMed  CAS  Google Scholar 

  • Kayed R., Head E., Thompson J. L., et al. (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486–489.

    Article  PubMed  CAS  Google Scholar 

  • Kuo W. L., Gehm B. D., Rosner M. R., Li W., and Keller G. (1994) Inducible expression and cellular localization of insulin-degrading enzyme in a stably transfected cell line. J. Biol. Chem. 269, 22599–22606.

    PubMed  CAS  Google Scholar 

  • Kuo W. L., Montag A. G., and Rosner M. R. (1993) Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues. Endocrinology 132, 604–611.

    Article  PubMed  CAS  Google Scholar 

  • Kuo Y. M., Kokjohn T. A., Beach T. G., et al. (2001) Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer’s disease brains. J. Biol. Chem. 276, 12991–12998.

    Article  PubMed  CAS  Google Scholar 

  • Kurochkin I. V. (2001) Insulin-degrading enzyme: embarking on amyloid destruction. Trends Biochem. Sci. 26, 421–425.

    Article  PubMed  CAS  Google Scholar 

  • Kurochkin I. V. and Goto S. (1994) Alzheimer’s β-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett. 345, 33–37.

    Article  PubMed  CAS  Google Scholar 

  • Kuusisto J., Koivisto K., Mykkanen L., et al. (1997) Association between features of the insulin resistance syndrome and Alzheimer’s disease independently of apolipoprotein E4 phenotype: cross sectional population based study. BMJ 315, 1045–1049.

    PubMed  CAS  Google Scholar 

  • Lauer D., Reichenbach A., and Birkenmeier G. (2001) Alpha 2-macroglobulin-mediated degradation of amyloid beta 1—42: a mechanism to enhance amyloid beta catabolism. Exp. Neurol. 167, 385–392.

    Article  PubMed  CAS  Google Scholar 

  • LeBlanc A. (1995) Increased production of 4 kDa amyloid β peptide in serum deprived human primary neuron cultures: possible involvement of apoptosis. J. Neurosci. 15, 7837–7846.

    PubMed  CAS  Google Scholar 

  • Lemere, C. A., Spooner, E. T., LaFrancois, J., et al. (2003) Evidence for peripheral clearance of cerebral Aβ protein following chronic, active Aβ immunization in PSAPP mice. Neurobiol. Dis. 14, 10–18.

    Article  PubMed  CAS  Google Scholar 

  • Li Y. J., Scott W. K., Hedges D. J., et al. (2002) Age at onset in two common neurodegenerative diseases is genetically controlled. Am. J. Hum. Genet. 70, 985–993.

    Article  PubMed  CAS  Google Scholar 

  • Lucius R., Sievers J., and Mentlein R. (1995) Enkephalin metabolism by microglial aminopeptidase N (CD13). J. Neurochem. 64, 1841–1847.

    Article  PubMed  CAS  Google Scholar 

  • Marr R. A., Rockenstein E., Mukherjee A., et al. (2003) Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. J. Neurosci. 23, 1992–1996.

    PubMed  CAS  Google Scholar 

  • Matsuoka Y., Saito M., LaFrancois J., et al. (2003) Novel therapeutic approach for the treatment of Alzheimer’s disease by peripheral administration of agents with an affinity to beta-amyloid. J. Neurosci. 23, 29–33.

    PubMed  CAS  Google Scholar 

  • McDermott J. R. and Gibson A. M. (1997) Degradation of Alzheimer’s beta-amyloid protein by human and rat brain peptidases: involvement of insulin-degrading enzyme. Neurochem. Res. 22, 49–56.

    Article  PubMed  CAS  Google Scholar 

  • Mentlein R., Ludwig R., and Martensen I. (1998) Proteolytic degradation of Alzheimer’s disease amyloid beta-peptide by a metalloproteinase from microglia cells. J. Neurochem. 70, 721–726.

    Article  PubMed  CAS  Google Scholar 

  • Miller B. C., Eckman E. A., Sambamurti K., et al. (2003) Amyloid-β peptide levels in brain are inversely correlated with insulin activity levels in vivo. Proc. Natl. Acad. Sci. USA 10,6221–6226.

    Article  CAS  Google Scholar 

  • Mohajeri M. H., Wollmer M. A., and Nitsch R. M. (2002) Abeta 42-induced increase in neprilysin is associated with prevention of amyloid plaque formation in vivo. J. Biol. Chem. 277, 35460–35465.

    Article  PubMed  CAS  Google Scholar 

  • Morgan D., Diamond D. M., Gottschall P. E., et al. (2000) A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature 408, 982–985.

    Article  PubMed  CAS  Google Scholar 

  • Morita M., Kurochkin I. V., Motojima K., et al. (2000) Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized proteins. Cell Struct. Funct. 25, 309–315.

    Article  PubMed  CAS  Google Scholar 

  • Mucke L., Masliah E., Yu G. Q., et al. (2000) High-level neuronal expression of abeta 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058.

    PubMed  CAS  Google Scholar 

  • Mukherjee A., Song E., Kihiko-Ehmann M., et al. (2000) Insulysin hydrolyzes amyloid beta peptides to products that are neither neurotoxic nor deposit on amyloid plaques. J. Neurosci. 20, 8745–8749.

    PubMed  CAS  Google Scholar 

  • Mukherjee A. and Hersh L. B. (2002) Regulation of amyloid β-peptide levels by enzymatic degradation. J Alzheimer Dis. 4, 341–348.

    CAS  Google Scholar 

  • Myers A., Holmans P., Marshall H., et al. (2000) Susceptibility locus for Alzheimer’s disease on chromosome 10. Science 290, 2304–2305.

    Article  PubMed  CAS  Google Scholar 

  • Nakagomi S., Kiryu-Seo S., and Kiyama H. (2000) Endothelin-converting enzymes and endothelin receptor B messenger RNAs are expressed in different neural cell species and these messenger RNAs are coordinately induced in neurons and astrocytes respectively following nerve injury. Neuroscience 101, 441–449.

    Article  PubMed  CAS  Google Scholar 

  • Ott A., Stolk R. P., van Harskamp F., Pols H. A., Hofman A., and Breteler M. M. (1999) Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 53, 1937–1942.

    PubMed  CAS  Google Scholar 

  • Perez A., Morelli L., Cresto J. C., and Castano E. M. (2000) Degradation of soluble amyloid beta-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.

    Article  PubMed  CAS  Google Scholar 

  • Price D. L. and Sisodia S. S. (1998) Mutant genes in familial Alzheimer’s disease and transgenic models. Annu. Rev. Neurosci. 21, 479–505.

    Article  PubMed  CAS  Google Scholar 

  • Qiu W. Q., Walsh D. M., Ye Z., et al. (1998) Insulin-degrading enzyme regulates extracellular levels of amyloid β-protein by degradation. J. Biol. Chem. 273, 32730–32738.

    Article  PubMed  CAS  Google Scholar 

  • Rockenstein E., Mallory M., Mante M., Sisk A., and Masliah E. (2001) Early formation of mature amyloid-beta protein deposits in a mutant APP transgenic model depends on levels of Abeta(1-42). J. Neurosci. Res. 66, 573–582.

    Article  PubMed  CAS  Google Scholar 

  • Sato M., Ikeda K., Haga S., Allsop D., and Ishii T. (1991) A monoclonal antibody to common acute lymphoblastic leukemia antigen (neutral endopeptidase) immunostains senile plaques in the brains of patients with Alzheimer’s disease. Neurosci. Lett. 121, 271–273.

    Article  PubMed  CAS  Google Scholar 

  • Savage M. J., Trusko S. P., Howland D. S., et al. (1998) Turnover of amyloid β-protein in mouse brain and acute reduction of its level by phorbol ester. J. Neurosci. 18, 1743–1752.

    PubMed  CAS  Google Scholar 

  • Schenk D., Barbour R., Dunn W., et al. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173–177.

    Article  PubMed  CAS  Google Scholar 

  • Schenk D. B. and Yednock T. (2002) The role of microglia in Alzheimer’s disease: friend or foe? Neurobiol. Aging 23, 677–679.

    Article  PubMed  CAS  Google Scholar 

  • Selkoe D. J. (2001) Clearing the brain’s amyloid cobwebs. Neuron 32, 177–180.

    Article  PubMed  CAS  Google Scholar 

  • Seta K. A. and Roth R. A. (1997) Overexpression of insulin degrading enzyme: cellular localization and effects on insulin signaling. Biochem. Biophys. Res. Commun. 231, 167–171.

    Article  PubMed  CAS  Google Scholar 

  • Shibata M., Yamada S., Kumar, S. R., 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.

    Article  PubMed  CAS  Google Scholar 

  • Shipp M. A., Stefano G. B., Switzer S. N., Griffin J. D., and Reinherz E. L. (1991) CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation. Blood 78, 1834–1841.

    PubMed  CAS  Google Scholar 

  • Shirotani K., Tsubuki S., Iwata N., et al. (2001) Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases. J. Biol. Chem. 276, 21895–21901.

    Article  PubMed  CAS  Google Scholar 

  • Sudoh S., Frosch M. P., and Wolf B. A. (2002) Differential effects of proteases involved in intracellular degradation of amyloid beta-protein between detergent-soluble and -insoluble pools in CHO-695 cells. Biochemistry 41, 1091–1099.

    Article  PubMed  CAS  Google Scholar 

  • Tanzi R. E. and Bertram L. (2001) New frontiers in Alzheimer’s disease genetics. Neuron 32, 181–184.

    Article  PubMed  CAS  Google Scholar 

  • Turner A. J., Isaac R. E., and Coates D. (2001) The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Bioessays 23, 261–269.

    Article  PubMed  CAS  Google Scholar 

  • Turner A. J., and Tanzawa K. (1997) Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. Faseb. J. 11, 355–364.

    PubMed  CAS  Google Scholar 

  • Vekrellis K., Ye Z., Qiu W. Q., et al. (2000) Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J. Neurosci. 20, 1657–1665.

    PubMed  CAS  Google Scholar 

  • Walsh D. M., Klyubin I., Fadeeva J. V., et al. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539.

    Article  PubMed  CAS  Google Scholar 

  • Wyss-Coray T., Lin C., Yan F., et al. (2001) TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat. Med. 7, 612–618.

    Article  PubMed  CAS  Google Scholar 

  • Wyss-Coray T., Loike J. D., Brionne T. C., et al. (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat. Med. 9, 453–457.

    Article  PubMed  CAS  Google Scholar 

  • Yasojima K., Akiyama H., McGeer E. G., and McGeer, P. L. (2001) Reduced neprilysin in high plaqueareas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide. Neurosci. Lett. 297, 97–100.

    Article  PubMed  CAS  Google Scholar 

  • Zhao W. and Alkon D. L. (2001) Role of insulin and insulin receptor in learning and memory. Mol. Cell. Endocrinol. 177, 125–134.

    Article  PubMed  CAS  Google Scholar 

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  1. Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital East, 114 16th St., 02129-4404, Charlestown, MA

    Suzanne Y. Guénette

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Guénette, S.Y. Mechanisms of Aβ clearance and catabolism. Neuromol Med 4, 147–160 (2003). https://doi.org/10.1385/NMM:4:3:147

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