Cholesterol twists the transmembrane Di-Gly region of amyloid-precursor protein.

ABSTRACT: Nearly 95% of Alzheimer's disease (AD) occurs sporadically without genetic linkage. Aging, hypertension, high cholesterol content, and diabetes are known nongenomic risk factors of AD. Aggregation of Aβ peptides is an initial event of AD pathogenesis. Aβ peptides are catabolic products of a type I membrane protein called amyloid precursor protein (APP). Aβ40 is the major product, whereas the 2-residue-longer version, Aβ42, induces amyloid plaque formation in the AD brain. Since cholesterol content is one risk factor for sporadic AD, we aimed to explore whether cholesterol in the membrane affects the structure of the APP transmembrane region, thereby modulating the γ-secretase cutting behavior. Here, we synthesized several peptides containing the APP transmembrane region (sequence 693-726,

SUBMITTER: Wang DT 

PROVIDER: S-EPMC10230161 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature