The Catalytic Core of γ-Secretase: Presenilin Revisited

Author(s): Harald Steiner.

Journal Name: Current Alzheimer Research

Volume 5 , Issue 2 , 2008

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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

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Article Details

VOLUME: 5
ISSUE: 2
Year: 2008
Page: [147 - 157]
Pages: 11
DOI: 10.2174/156720508783954677
Price: $58

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