Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts.

ABSTRACT: A major characteristic of Alzheimer's disease (AD) is the accumulation of misfolded amyloid-β (Aβ) peptide. Several studies linked AD with type 2 diabetes due to similarities between Aβ and human amylin. This study investigates the effect of amylin and pramlintide on Aβ pathogenesis and the predisposing molecular mechanism(s) behind the observed effects in TgSwDI mouse, a cerebral amyloid angiopathy (CAA) and AD model. Our findings showed that thirty days of intraperitoneal injection with amylin or pramlintide increased Aβ burden in mice brains. Mechanistic studies revealed both peptides altered the amyloidogenic pathway and increased Aβ production by modulating amyloid precursor protein (APP) and γ-secretase levels in lipid rafts. In addition, both peptides increased levels of B4GALNT1 en

SUBMITTER: Mousa YM 

PROVIDER: S-EPMC7048857 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature