An aminosterol breaks the autocatalytic cycle of Aβ₄₂ aggregation and protects cell membranes from its soluble aggregates.

ABSTRACT: Aberrant aggregates of the 42-residue form of the amyloid-β peptide (Aβ₄₂) are cytotoxic in Alzheimer's disease (AD). Cost-effective and chronically safe disease-modifying therapeutics are needed to address the AD medical emergency worldwide. To increase our understanding of the mechanisms of Aβ₄₂-induced cytotoxicity and to investigate clinically relevant aminosterols, we study the impact of claramine on the aggregation kinetics and properties of Aβ₄₂ aggregates, as well as the ability of these proteotoxic species to bind and disrupt cell membranes. Whereas previously studied aminosterols accelerated Aβ₄₂ aggregation, we show that claramine potently inhibits Aβ₄₂ amyloid fibril formation. We find that claramine stabilizes soluble Aβ

SUBMITTER: Fallot LB 

PROVIDER: S-EPMC12280974 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature