Mechanisms for the Insertion of Toxic, Fibril-like β-Amyloid Oligomers into the Membrane.

ABSTRACT: Amyloid-β (Aβ) oligomers destabilize cellular ionic homeostasis, mediating Alzheimer's disease (AD). It is still unclear whether the mechanism (i) is mediated by cell surface receptors; (ii) is direct, with Aβ oligomers interacting with membrane lipids; or (iii) both mechanisms take place. Recent studies indicate that Aβ oligomers may act by either of the last two. Little is known about the oligomers' structures and how they spontaneously insert into the membrane. Using explicit solvent molecular dynamics (MD) simulations, we show that fibril-like Aβ(17-42) (p3) oligomer is capable of penetrating the membrane. Insertion is similar to that observed for protegrin-1 (PG-1), a cytolytic β-sheet-rich antimicrobial peptide (AMP). Both Aβ and PG-1 favor the amphipathic interface of the lipid bila

SUBMITTER: Jang H 

PROVIDER: S-EPMC3539805 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature