Speaker
Description
ABSTRACT: Amyloid β (Aβ) aggregation on neuronal membranes is a key event in the pathogenesis of Alzheimer’s disease. Among Aβ isoforms, Aβ42 is particularly pathogenic due to its rapid aggregation and high cytotoxicity. Ganglioside GM1, a glycosphingolipid enriched in neuronal membranes, can form nanoclusters that strongly bind Aβ and induce membrane-associated aggregation. Upon binding to GM1 clusters, Aβ undergoes a structural transition from a random coil to an α-helix-rich conformation, initiating fibril formation. Notably, Aβ fibrils formed on GM1-containing membranes adopt antiparallel β-sheet structures, which are more cytotoxic than the parallel β-sheets typically formed in solution.
In this study, we use nanoscale molecular dynamics simulations to investigate the molecular interactions between Aβ42 and GM1-containing membranes. By comparing systems with and without GM1, we reveal how GM1 clusters modulate Aβ42 conformational landscapes and promote early aggregation events. Our results provide atomistic insights into the membrane-mediated mechanisms that drive pathogenic Aβ aggregation.
