Skip to main content

Advertisement

SpringerLink
Log in

Regulation of alpha-secretase ADAM10 expression and activity

  • Review
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The amyloid precursor protein (APP) has a pivotal role in pathogenesis of Alzheimer’s disease (AD) via its beta- and gamma-secretase-derived cleavage products—the A-beta peptides. An alternative processing pathway provided by the alpha-secretase prevents formation of those toxic peptides and gives rise to the neurotrophic and neuroprotective cleavage product APPs-alpha. The molecular identity of the alpha-secretase has been confirmed recently, and there is consistency about ADAM10 being the most relevant and physiological enzyme of this class. It is not clear to what extent a deficiency in the catalytic activity of ADAM10 contributes to AD pathology and whether a decline occurs in aging humans. Nevertheless, ADAM10 has been suggested as a valuable target for prevention and/or for treatment of Alzheimer’s disease. This review focuses on our knowledge about regulation of ADAM10 on different levels of cell physiology, such as transcription and translation, as well as protein–protein interactions and how this especially in the case of transcriptional regulation by retinoic acids might lead to the development of new therapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ahmed RR, Holler CJ, Webb RL, Li F, Beckett TL, Murphy MP (2010) BACE1 and BACE2 enzymatic activities in Alzheimer’s disease. J Neurochem 112:1045–1053

    Article  PubMed  CAS  Google Scholar 

  • Anders A, Gilbert S, Garten W, Postina R, Fahrenholz F (2001) Regulation of the alpha-secretase ADAM10 by its prodomain and proprotein convertases. FASEB J 15:1837–1839

    PubMed  CAS  Google Scholar 

  • Armstrong JL, Ruiz M, Boddy AV, Redfern CP, Pearson AD, Veal GJ (2005) Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells. Br J Cancer 92:696–704

    Article  PubMed  CAS  Google Scholar 

  • Bai S, Nasser MW, Wang B, Hsu SH, Datta J, Kutay H, Yadav A, Nuovo G, Kumar P, Ghoshal K (2009) MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 284:32015–32027

    Article  PubMed  CAS  Google Scholar 

  • Bekris LM, Galloway NM, Millard S, Lockhart D, Li G, Galasko DR, Farlow MR, Clark CM, Quinn JF, Kaye JA, Schellenberg GD, Leverenz JB, Seubert P, Tsuang DW, Peskind ER, Yu CE (2011) Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer’s disease. Neurobiol Aging 32:556.e13–556.e23

    Article  CAS  Google Scholar 

  • Belyaev ND, Kellett KA, Beckett C, Makova NZ, Revett TJ, Nalivaeva NN, Hooper NM, Turner AJ (2010) The transcriptionally active amyloid precursor protein (APP) intracellular domain is preferentially produced from the 695 isoform of APP in a {beta}-secretase-dependent pathway. J Biol Chem 285:41443–41454

    Article  PubMed  CAS  Google Scholar 

  • Bernstein HG, Bukowska A, Krell D, Bogerts B, Ansorge S, Lendeckel U (2003) Comparative localization of ADAMs 10 and 15 in human cerebral cortex normal aging, Alzheimer disease and Down syndrome. J Neurocytol 32:153–160

    Article  PubMed  CAS  Google Scholar 

  • Buxbaum JD, Liu KN, Luo Y, Slack JL, Stocking KL, Peschon JJ, Johnson RS, Castner BJ, Cerretti DP, Black RA (1998) Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 273:27765–27767

    Article  PubMed  CAS  Google Scholar 

  • Cai Y, Xiong K, Zhang XM, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Chu Y, Kordower JH, Yan XX (2010) β-Secretase-1 elevation in aged monkey and Alzheimer’s disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and beta-amyloid accumulation. Eur J Neurosci 32:1223–1238

    Article  PubMed  Google Scholar 

  • Cattabeni F, Colciaghi F, Di Luca M (2004) Platelets provide human tissue to unravel pathogenic mechanisms of Alzheimer disease. Prog Neuropsychopharmacol Biol Psychiatry 28:763–770

    Article  PubMed  CAS  Google Scholar 

  • Cisse MA, Sunyach C, Lefranc-Jullien S, Postina R, Vincent B, Checler F (2005) The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. J Biol Chem 280:40624–40631

    Article  PubMed  CAS  Google Scholar 

  • Colciaghi F, Borroni B, Pastorino L, Marcello E, Zimmermann M, Cattabeni F, Padovani A, Di Luca M (2002) [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients. Mol Med 8:67–74

    PubMed  CAS  Google Scholar 

  • Corrigan F, Pham CL, Vink R, Blumbergs PC, Masters CL, van den Heuvel C, Cappai R (2011) The neuroprotective domains of the amyloid precursor protein, in traumatic brain injury, are located in the two growth factor domains. Brain Res 1378:137–143

    Article  PubMed  CAS  Google Scholar 

  • Coulson DT, Beyer N, Quinn JG, Brockbank S, Hellemans J, Irvine GB, Ravid R, Johnston JA (2010) BACE1 mRNA expression in Alzheimer’s disease postmortem brain tissue. J Alzheimers Dis 22:1111–1122

    PubMed  CAS  Google Scholar 

  • Deuss M, Reiss K, Hartmann D (2008) Part-time alpha-secretases: the functional biology of ADAM 9, 10 and 17. Curr Alzheimer Res 5:187–201

    Article  PubMed  CAS  Google Scholar 

  • Donmez G, Wang D, Cohen DE, Guarente L (2010) SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 142:320–332

    Article  PubMed  CAS  Google Scholar 

  • Endres K, Fahrenholz F (2010) Upregulation of the alpha-secretase ADAM10—risk or reason for hope? FEBS J 277:1585–1596

    Article  PubMed  CAS  Google Scholar 

  • Endres K, Anders A, Kojro E, Gilbert S, Fahrenholz F, Postina R (2003) Tumor necrosis factor-alpha converting enzyme is processed by proprotein-convertases to its mature form which is degraded upon phorbol ester stimulation. Eur J Biochem 270:2386–2393

    Article  PubMed  CAS  Google Scholar 

  • Endres K, Postina R, Schroeder A, Mueller U, Fahrenholz F (2005) Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases. FEBS J 272:5808–5820

    Article  PubMed  CAS  Google Scholar 

  • Epis R, Gardoni F, Marcello E, Genazzani A, Canonico PL, Di Luca M (2010) Searching for new animal models of Alzheimer’s disease. Eur J Pharmacol 626:57–63

    Article  PubMed  CAS  Google Scholar 

  • Escrevente C, Morais VA, Keller S, Soares CM, Altevogt P, Costa J (2008) Functional role of N-glycosylation from ADAM10 in processing, localization and activity of the enzyme. Biochim Biophys Acta 1780:905–913

    Article  PubMed  CAS  Google Scholar 

  • Ewers M, Zhong Z, Burger K, Wallin A, Blennow K, Teipel SJ, Shen Y, Hampel H (2008) Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in subjects with mild cognitive impairment and Alzheimer’s disease. Brain 131:1252–1258

    Article  PubMed  Google Scholar 

  • Fahrenholz F (2007) Alpha-secretase as a therapeutic target. Curr Alzheimer Res 4:412–417

    Article  PubMed  CAS  Google Scholar 

  • Fellgiebel A, Kojro E, Muller MJ, Scheurich A, Schmidt LG, Fahrenholz F (2009) CSF APPs alpha and phosphorylated tau protein levels in mild cognitive impairment and dementia of Alzheimer’s type. J Geriatr Psychiatry Neurol 22:3–9

    Article  PubMed  Google Scholar 

  • Fluhrer R, Capell A, Westmeyer G, Willem M, Hartung B, Condron MM, Teplow DB, Haass C, Walter J (2002) A non-amyloidogenic function of BACE-2 in the secretory pathway. J Neurochem 81:1011–1020

    Article  PubMed  CAS  Google Scholar 

  • Freese C, Garratt AN, Fahrenholz F, Endres K (2009) The effects of alpha-secretase ADAM10 on the proteolysis of neuregulin-1. FEBS J 276:1568–1580

    Article  PubMed  CAS  Google Scholar 

  • Fukumoto H, Cheung BS, Hyman BT, Irizarry MC (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 59:1381–1389

    Article  PubMed  Google Scholar 

  • Gatta LB, Albertini A, Ravid R, Finazzi D (2002) Levels of beta-secretase BACE and alpha-secretase ADAM10 mRNAs in Alzheimer hippocampus. Neuroreport 13:2031–2033

    Article  PubMed  CAS  Google Scholar 

  • Gibb DR, El SM, Kang DJ, Rowe WJ, El SR, Cichy J, Yagita H, Tew JG, Dempsey PJ, Crawford HC, Conrad DH (2010) ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. J Exp Med 207:623–635

    Article  PubMed  CAS  Google Scholar 

  • Gibb DR, Saleem SJ, Chaimowitz NS, Mathews J, Conrad DH (2011) The emergence of ADAM10 as a regulator of lymphocyte development and autoimmunity. Mol Immunol 48:1319–1327

    Article  PubMed  CAS  Google Scholar 

  • Goodger ZV, Rajendran L, Trutzel A, Kohli BM, Nitsch RM, Konietzko U (2009) Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway. J Cell Sci 122:3703–3714

    Article  PubMed  CAS  Google Scholar 

  • Gorham P, Bark N, Bjorkhem I, Meaney S, Crisby M (2010) Platelet alpha- and beta- secretase activities are not significantly affected by dementia or mild cognitive impairment in Swedish patients. Curr Alzheimer Res 7:134–139

    Article  PubMed  CAS  Google Scholar 

  • Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Gast D, Joumaa S, Zentgraf H, Fogel M, Altevogt DP (2003) ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles. FASEB J 17:292–294

    PubMed  CAS  Google Scholar 

  • Harada H, Tamaoka A, Ishii K, Shoji S, Kametaka S, Kametani F, Saito Y, Murayama S (2006) Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer’s disease brains. Neurosci Res 54:24–29

    Article  PubMed  CAS  Google Scholar 

  • Harris B, Pereira I, Parkin E (2009) Targeting ADAM10 to lipid rafts in neuroblastoma SH-SY5Y cells impairs amyloidogenic processing of the amyloid precursor protein. Brain Res 1296:203–215

    Article  PubMed  CAS  Google Scholar 

  • Hock C, Golombowski S, Muller-Spahn F, Naser W, Beyreuther K, Monning U, Schenk D, Vigo-Pelfrey C, Bush AM, Moir R, Tanzi RE, Growdon JH, Nitsch RM (1998) Cerebrospinal fluid levels of amyloid precursor protein and amyloid beta-peptide in Alzheimer’s disease and major depression—inverse correlation with dementia severity. Eur Neurol 39:111–118

    Article  PubMed  CAS  Google Scholar 

  • Holsinger RM, McLean CA, Beyreuther K, Masters CL, Evin G (2002) Increased expression of the amyloid precursor beta-secretase in Alzheimer’s disease. Ann Neurol 51:783–786

    Article  PubMed  CAS  Google Scholar 

  • Jarvis CI, Goncalves MB, Clarke E, Dogruel M, Kalindjian SB, Thomas SA, Maden M, Corcoran JP (2010) Retinoic acid receptor-alpha signalling antagonizes both intracellular and extracellular amyloid-beta production and prevents neuronal cell death caused by amyloid-beta. Eur J Neurosci 32:1246–1255

    Article  PubMed  CAS  Google Scholar 

  • Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I, Bartsch U, Weskamp G, Blobel CP, Glatzel M, De SB, Saftig P (2010) The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J Neurosci 30:4833–4844

    Article  PubMed  CAS  Google Scholar 

  • Kawahara K, Nishi K, Suenobu M, Ohtsuka H, Maeda A, Nagatomo K, Kuniyasu A, Staufenbiel M, Nakagomi M, Shudo K, Nakayama H (2009) Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain beta-amyloid peptides in APP23 mice. Biol Pharm Bull 32:1307–1309

    Article  PubMed  CAS  Google Scholar 

  • Koike H, Tomioka S, Sorimachi H, Saido TC, Maruyama K, Okuyama A, Fujisawa-Sehara A, Ohno S, Suzuki K, Ishiura S (1999) Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein. Biochem J 343(Pt 2):371–375

    Article  PubMed  CAS  Google Scholar 

  • Kojro E, Fahrenholz F (2005) The non-amyloidogenic pathway: structure and function of alpha-secretases. Subcell Biochem 38:105–127

    Article  PubMed  CAS  Google Scholar 

  • Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10. Proc Natl Acad Sci USA 98:5815–5820

    Article  PubMed  CAS  Google Scholar 

  • Kojro E, Postina R, Buro C, Meiringer C, Gehrig-Burger K, Fahrenholz F (2006) The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein. FASEB J 20:512–514

    PubMed  CAS  Google Scholar 

  • Kojro E, Fuger P, Prinzen C, Kanarek AM, Rat D, Endres K, Fahrenholz F, Postina R (2010) Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by suppression of cholesterol synthesis. J Alzheimers Dis 20:1215–1231

    PubMed  CAS  Google Scholar 

  • Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S, Lichtenthaler SF (2010) ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 29:3020–3032

    Article  PubMed  CAS  Google Scholar 

  • Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F (1999) Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 96:3922–3927

    Article  PubMed  CAS  Google Scholar 

  • Lammich S, Buell D, Zilow S, Ludwig AK, Nuscher B, Lichtenthaler SF, Prinzen C, Fahrenholz F, Haass C (2010) Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 5′-untranslated region. J Biol Chem 285:15753–15760

    Article  PubMed  CAS  Google Scholar 

  • Lannfelt L, Basun H, Wahlund LO, Rowe BA, Wagner SL (1995) Decreased alpha-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer’s disease. Nat Med 1:829–832

    Article  PubMed  CAS  Google Scholar 

  • Lee CS, Koo J (2005) A review of acitretin, a systemic retinoid for the treatment of psoriasis. Expert Opin Pharmacother 6:1725–1734

    Article  PubMed  CAS  Google Scholar 

  • Li R, Lindholm K, Yang LB, Yue X, Citron M, Yan R, Beach T, Sue L, Sabbagh M, Cai H, Wong P, Price D, Shen Y (2004) Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer’s disease patients. Proc Natl Acad Sci USA 101:3632–3637

    Article  PubMed  CAS  Google Scholar 

  • Marcello E, Gardoni F, Mauceri D, Romorini S, Jeromin A, Epis R, Borroni B, Cattabeni F, Sala C, Padovani A, Di Luca M (2007) Synapse-associated protein-97 mediates alpha-secretase ADAM10 trafficking and promotes its activity. J Neurosci 27:1682–1691

    Article  PubMed  CAS  Google Scholar 

  • Marcello E, Gardoni F, Di Luca M, Perez-Otano I (2010) An arginine stretch limits ADAM10 exit from the endoplasmic reticulum. J Biol Chem 285:10376–10384

    Article  PubMed  CAS  Google Scholar 

  • Marcello E, Epis R, Saraceno C, Gardoni F, Borroni B, Cattabeni F, Padovani A, Di Luca M (2011) SAP97-mediated local trafficking is altered in Alzheimer disease patients’ hippocampus. Neurobiol Aging (in press)

  • Marcinkiewicz M, Seidah NG (2000) Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. J Neurochem 75:2133–2143

    Article  PubMed  CAS  Google Scholar 

  • Matthews V, Schuster B, Schutze S, Bussmeyer I, Ludwig A, Hundhausen C, Sadowski T, Saftig P, Hartmann D, Kallen KJ, Rose-John S (2003) Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). J Biol Chem 278:38829–38839

    Article  PubMed  CAS  Google Scholar 

  • McGuinness B, Passmore P (2010) Can statins prevent or help treat Alzheimer’s disease? J Alzheimers Dis 20:925–933

    PubMed  Google Scholar 

  • Merlos-Suarez A, Fernandez-Larrea J, Reddy P, Baselga J, Arribas J (1998) Pro-tumor necrosis factor-alpha processing activity is tightly controlled by a component that does not affect notch processing. J Biol Chem 273:24955–24962

    Article  PubMed  CAS  Google Scholar 

  • Miners JS, van Helmond Z, Kehoe PG, Love S (2010) Changes with age in the activities of beta-secretase and the Aβ-degrading enzymes neprilysin, insulin-degrading enzyme and angiotensin-converting enzyme. Brain Pathol 20:794–802

    Article  PubMed  CAS  Google Scholar 

  • Miwako I, Kagechika H (2007) Tamibarotene. Drugs Today (Barc) 43:563–568

    Article  CAS  Google Scholar 

  • Mulder SD, van der Flier WM, Verheijen JH, Mulder C, Scheltens P, Blankenstein MA, Hack CE, Veerhuis R (2010) BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology. J Alzheimers Dis 20:253–260

    PubMed  CAS  Google Scholar 

  • Olsson A, Hoglund K, Sjogren M, Andreasen N, Minthon L, Lannfelt L, Buerger K, Moller HJ, Hampel H, Davidsson P, Blennow K (2003) Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients. Exp Neurol 183:74–80

    Article  PubMed  CAS  Google Scholar 

  • Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M (2004) Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro. Exp Neurol 189:380–392

    Article  PubMed  CAS  Google Scholar 

  • Parkin E, Harris B (2009) A disintegrin and metalloproteinase (ADAM)-mediated ectodomain shedding of ADAM10. J Neurochem 108:1464–1479

    Article  PubMed  CAS  Google Scholar 

  • Patel NV, Gordon MN, Connor KE, Good RA, Engelman RW, Mason J, Morgan DG, Morgan TE, Finch CE (2005) Caloric restriction attenuates Abeta-deposition in Alzheimer transgenic models. Neurobiol Aging 26:995–1000

    Article  PubMed  CAS  Google Scholar 

  • Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456–1464

    PubMed  CAS  Google Scholar 

  • Prinzen C, Muller U, Endres K, Fahrenholz F, Postina R (2005) Genomic structure and functional characterization of the human ADAM10 promoter. FASEB J 19:1522–1524

    PubMed  CAS  Google Scholar 

  • Prinzen C, Trumbach D, Wurst W, Endres K, Postina R, Fahrenholz F (2009) Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice. BMC Genomics 10:66

    Article  PubMed  Google Scholar 

  • Prior R, Monning U, Schreiter-Gasser U, Weidemann A, Blennow K, Gottfries CG, Masters CL, Beyreuther K (1991) Quantitative changes in the amyloid beta A4 precursor protein in Alzheimer cerebrospinal fluid. Neurosci Lett 124:69–73

    Article  PubMed  CAS  Google Scholar 

  • Pruessmeyer J, Ludwig A (2009) The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer. Semin Cell Dev Biol 20:164–174

    Article  PubMed  CAS  Google Scholar 

  • Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM (2006) Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem 281:21745–21754

    Article  PubMed  CAS  Google Scholar 

  • Rat D, Schmitt U, Tippmann F, Dewachter I, Theunis C, Wieczerzak E, Postina R, van Leuven F, Fahrenholz F, Kojro E (2011) Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer’s disease-like pathology in amyloid precursor protein-transgenic mice. FASEB J 25(9):3208–3218

    Google Scholar 

  • Reiss K, Saftig P (2009) The “a disintegrin and metalloprotease” (ADAM) family of sheddases: physiological and cellular functions. Semin Cell Dev Biol 20:126–137

    Article  PubMed  CAS  Google Scholar 

  • Roghani M, Becherer JD, Moss ML, Atherton RE, Erdjument-Bromage H, Arribas J, Blackburn RK, Weskamp G, Tempst P, Blobel CP (1999) Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic activity. J Biol Chem 274:3531–3540

    Article  PubMed  CAS  Google Scholar 

  • Sala Frigerio C, Fadeeva JV, Minogue AM, Citron M, van Leuven F, Staufenbiel M, Paganetti P, Selkoe DJ, Walsh DM (2010) beta-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins. FEBS J 277:1503–1518

    Google Scholar 

  • Schettini G, Govoni S, Racchi M, Rodriguez G (2010) Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role—relevance for Alzheimer pathology. J Neurochem 115:1299–1308

    Article  PubMed  CAS  Google Scholar 

  • Sennvik K, Fastbom J, Blomberg M, Wahlund LO, Winblad B, Benedikz E (2000) Levels of alpha- and beta-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer’s disease patients. Neurosci Lett 278:169–172

    Article  PubMed  CAS  Google Scholar 

  • Skovronsky DM, Moore DB, Milla ME, Doms RW, Lee VM (2000) Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. J Biol Chem 275:2568–2575

    Article  PubMed  CAS  Google Scholar 

  • Slack BE, Ma LK, Seah CC (2001) Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated by tumour necrosis factor-alpha converting enzyme. Biochem J 357:787–794

    Article  PubMed  CAS  Google Scholar 

  • Tang K, Hynan LS, Baskin F, Rosenberg RN (2006) Platelet amyloid precursor protein processing: a bio-marker for Alzheimer’s disease. J Neurol Sci 240:53–58

    Article  PubMed  CAS  Google Scholar 

  • Thornton E, Vink R, Blumbergs PC, van den Heuvel C (2006) Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats. Brain Res 1094:38–46

    Article  PubMed  CAS  Google Scholar 

  • Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F (2009) Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J 23:1643–1654

    Article  PubMed  CAS  Google Scholar 

  • Tousseyn T, Thathiah A, Jorissen E, Raemaekers T, Konietzko U, Reiss K, Maes E, Snellinx A, Serneels L, Nyabi O, Annaert W, Saftig P, Hartmann D, De SB (2009) ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. J Biol Chem 284:11738–11747

    Article  PubMed  CAS  Google Scholar 

  • Tyler SJ, Dawbarn D, Wilcock GK, Allen SJ (2002) alpha- and beta-secretase: profound changes in Alzheimer’s disease. Biochem Biophys Res Commun 299:373–376

    Article  PubMed  CAS  Google Scholar 

  • Van Nostrand WE, Wagner SL, Shankle WR, Farrow JS, Dick M, Rozemuller JM, Kuiper MA, Wolters EC, Zimmerman J, Cotman CW (1992) Decreased levels of soluble amyloid beta-protein precursor in cerebrospinal fluid of live Alzheimer disease patients. Proc Natl Acad Sci USA 89:2551–2555

    Article  PubMed  Google Scholar 

  • Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286:735–741

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Ho L, Qin W, Rocher AB, Seror I, Humala N, Maniar K, Dolios G, Wang R, Hof PR, Pasinetti GM (2005) Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer’s disease. FASEB J 19:659–661

    Article  PubMed  Google Scholar 

  • Weskamp G, Cai H, Brodie TA, Higashyama S, Manova K, Ludwig T, Blobel CP (2002) Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life. Mol Cell Biol 22:1537–1544

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Sankaranarayanan S, Tugusheva K, Kahana J, Seabrook G, Shi XP, King E, Devanarayan V, Cook JJ, Simon AJ (2008) Decrease in age-adjusted cerebrospinal fluid beta-secretase activity in Alzheimer’s subjects. Clin Biochem 41:986–996

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki K, Mizui Y, Sagane K, Tanaka I (1997a) Assignment of a disintegrin and metalloproteinase domain 10 (Adam10) gene to mouse chromosome 9. Genomics 46:528–529

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki K, Mizui Y, Tanaka I (1997b) Radiation hybrid mapping of human ADAM10 gene to chromosome 15. Genomics 45:457–459

    Article  PubMed  CAS  Google Scholar 

  • Yang LB, Lindholm K, Yan R, Citron M, Xia W, Yang XL, Beach T, Sue L, Wong P, Price D, Li R, Shen Y (2003) Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat Med 9:3–4

    Article  PubMed  CAS  Google Scholar 

  • Zetterberg H, Andreasson U, Hansson O, Wu G, Sankaranarayanan S, Andersson ME, Buchhave P, Londos E, Umek RM, Minthon L, Simon AJ, Blennow K (2008) Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 65:1102–1107

    Article  PubMed  Google Scholar 

  • Zhao J, Fu Y, Yasvoina M, Shao P, Hitt B, O’Connor T, Logan S, Maus E, Citron M, Berry R, Binder L, Vassar R (2007) Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer’s disease pathogenesis. J Neurosci 27:3639–3649

    Article  PubMed  CAS  Google Scholar 

  • Zhong Z, Ewers M, Teipel S, Burger K, Wallin A, Blennow K, He P, McAllister C, Hampel H, Shen Y (2007) Levels of beta-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Arch Gen Psychiatry 64:718–726

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors’ own work is supported by the Federal Ministry of Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN, FKZ01GS08130). The clinical study concerning acitretin is kindly supported by the Alzheimer Forschungs initiative (AFI, PI A. Fellgiebel).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg-University Mainz, Untere Zahlbacher Str. 8, 55131, Mainz, Germany

    Kristina Endres & Falk Fahrenholz

Authors
  1. Kristina Endres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Falk Fahrenholz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristina Endres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Endres, K., Fahrenholz, F. Regulation of alpha-secretase ADAM10 expression and activity. Exp Brain Res 217, 343–352 (2012). https://doi.org/10.1007/s00221-011-2885-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-011-2885-7

Keywords

Search

Navigation