Abstract
Mutations in the presenilin 1 (PS1) gene are the major cause of familial Alzheimers disease (AD). They effect an increased production of the highly neurotoxic 42 amino acid variant of the amyloid-β peptide (Aβ), which is believed to initiate the disease. Aβ is the product of two consecutive cleavages of the β-amyloid precursor protein (APP) by two proteases, β-secretase and γ-secretase. The latter enzyme has been identified as an intramembrane-cleaving multiprotein complex that apart from APP cleaves a large number of other type I transmembrane proteins. PS1 and its homologue PS2 are essential for γ-secretase cleavage and more than a decade after their discovery it is now firmly established that they function as catalytic subunits of γ-secretase. This review recapitulates the findings that led to this conclusion as well as the further progress made on the function of PS as γ-secretase since then.
Keywords: Alzheimer's disease, Amyloid β-peptide, presenilin, γ-secretase
Current Alzheimer Research
Title: The Catalytic Core of γ-Secretase: Presenilin Revisited
Volume: 5 Issue: 2
Author(s): Harald Steiner
Affiliation:
Keywords: Alzheimer's disease, Amyloid β-peptide, presenilin, γ-secretase
Abstract: Mutations in the presenilin 1 (PS1) gene are the major cause of familial Alzheimers disease (AD). They effect an increased production of the highly neurotoxic 42 amino acid variant of the amyloid-β peptide (Aβ), which is believed to initiate the disease. Aβ is the product of two consecutive cleavages of the β-amyloid precursor protein (APP) by two proteases, β-secretase and γ-secretase. The latter enzyme has been identified as an intramembrane-cleaving multiprotein complex that apart from APP cleaves a large number of other type I transmembrane proteins. PS1 and its homologue PS2 are essential for γ-secretase cleavage and more than a decade after their discovery it is now firmly established that they function as catalytic subunits of γ-secretase. This review recapitulates the findings that led to this conclusion as well as the further progress made on the function of PS as γ-secretase since then.
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Cite this article as:
Steiner Harald, The Catalytic Core of γ-Secretase: Presenilin Revisited, Current Alzheimer Research 2008; 5 (2) . https://dx.doi.org/10.2174/156720508783954677
DOI https://dx.doi.org/10.2174/156720508783954677 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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