NSAID-based γ-secretase modulators do not bind to the amyloid-β polypeptide.

ABSTRACT: γ-Secretase modulators (GSMs) have received much attention as potential therapeutic agents for Alzheimer's disease (AD). GSMs increase the ratio between short and long forms of the amyloid-β (Aβ) polypeptides produced by γ-secretase and thereby decrease the amount of the toxic amyloid species. However, the mechanism of action of these agents is still poorly understood. One recent paper [Richter et al. (2010) Proc. Natl. Acad. Sci. U. S. A.107, 14597-14602] presented data that were interpreted to support direct binding of the GSM sulindac sulfide to Aβ(42), supporting the notion that GSM action is linked to direct binding of these compounds to the Aβ domain of its immediate precursor, the 99-residue C-terminal domain of the amyloid precursor protein (C99, also known as the β-CTF). Here, con

SUBMITTER: Barrett PJ 

PROVIDER: S-EPMC3272834 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature