Ganglioside GM1 slows down Aβ(1-42) aggregation by a primary nucleation inhibitory mechanism that is modulated by sphingomyelin and cholesterol.

ABSTRACT: The conversion of soluble amyloid-β peptides into fibrils is central in Alzheimer's disease. Lipids modulate amyloid-β aggregation, but whilst the mechanistic effect of individual lipid species is increasingly addressed, principles explaining their combinatorial contributions in biologically heterogenous membranes remain to be established. We used kinetic analyses to establish an inhibitory mechanism of GM1 gangliosides on the aggregation of amyloid-β variant Aβ(1-42) by which membrane-associated GM1 sequesters soluble Aβ(1-42) and retards primary nucleation. The kinetic inhibition increased in presence of the raft-enabling lipids cholesterol and sphingomyelin, although these lipids, intrinsically, catalysed primary and secondary nucleation respectively. These results decipher important tr

SUBMITTER: Sasanian N 

PROVIDER: S-EPMC12824409 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature