The Catalytic Core of γ-Secretase: Presenilin Revisited

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.

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