Designed Helical Peptides as Functional Probes for γ-Secretase.

ABSTRACT: γ-Secretase is a membrane-embedded aspartyl protease complex with presenilin as the catalytic component that cleaves within the transmembrane domain (TMD) of >90 known substrates, including the amyloid precursor protein (APP) of Alzheimer's disease. Processing by γ-secretase of the APP TMD produces the amyloid β-peptide (Aβ), including the 42-residue variant (Aβ42) that pathologically deposits in the Alzheimer brain. Complex proteolysis of APP substrate by γ-secretase involves initial endoproteolysis and subsequent carboxypeptidase trimming, resulting in two pathways of Aβ production: Aβ49 → Aβ46 → Aβ43 → Aβ40 and Aβ48 → Aβ45 → Aβ42 → Aβ38. Dominant mutations in APP and presenilin cause early onset familial Alzheimer's disease (FAD). Understanding how γ-secretase processing of APP is alter

SUBMITTER: Philip AT 

PROVIDER: S-EPMC7224395 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature