Abstract
The Aβ peptide is the principal component of amyloid plaques in the brain of Alzheimer’s Disease (AD) patients. Aβ is derived from β-Amyloid Precursor Protein (APP) by two sequential proteolytic events. Although APP proteolysis has been extensively studied because of its relevance to AD, its biologic function remains enigmatic. In this paper I propose a model in which processing of APP, under control of presenilins, generates an intracellular peptide that regulates the cellular threshold to apoptosis.
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References
Brown MS, Ye J, Rawson RB, Goldstein JL (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100: 391–398.
Price DL, Sisodia SS (1998) Mutant genes in familial Alzheimer’s disease and transgenic models. Annu Rev Neurosci 21:479–505.
De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) Prersenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522.
Haass C, De Strooper B (1999) The presenilins in Alzheimer’s disease. Proteolysis holds the key. Science 286:916–919.
Nishimoto I (1998) A new paradigm for neurotoxicity by FAD mutants of betaAPP: a signaling abnormality. Neurobiol Aging 1 (Suppl):S33–38.
Palacino JJ, Berechid BE, Alexander P, Eckman C, Younkin S, Nye JS, Wolozin B (2000) Regulation of amyloid precursor protein processing by presenilin 1 (PS1) andPS2 inPSl knockout cells. J Biol Chem 275:215–222.
Passer B, Pellegrini L, Russo C, Siegel RM, Lenardo MJ, Schettini G, Bachmann M, Tabaton M, D’Adamio L (2000) Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer’s β-amyloid precursor protein. J Alzheimer’s Dis 2(2(3,4)):289–301.
Price DL, Sisodia SS (1998) Mutant genes in familial Alzheimer’s disease and transgenic models. Annu Rev Neurosci 21:479–505.
Wolozin B, Iwasaki K, Vito P, Ganjei JK, Lacana E, Sunderland T, Zhao B, Kusiak JW, Wasco W, D’Adamio L (1996) Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 274:1710–1713.
Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (2000) Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407:48–54.
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© 2002 Springer-Verlag Berlin Heidelberg
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D’Adamio, L. (2002). βAPP Processing, its Biology and Alzheimer’s Disease. In: Christen, Y., Israël, A., De Strooper, B., Checler, F. (eds) Notch from Neurodevelopment to Neurodegeneration: Keeping the Fate. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55996-9_8
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DOI: https://doi.org/10.1007/978-3-642-55996-9_8
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62767-5
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