Angew Chem Int Ed Engl, 2016, 55(32):9411-9415

GM1Ganglioside Inhibits β-Amyloid Oligomerization Induced by Sphingomyelin

KGaA, Weinheim β-Amyloid (Aβ) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of Aβ oligomers in vivo. Membrane components sphingomyelin and GM1have been shown to promote aggregation of Aβ; however, these studies were performed under extreme, non-physiological conditions. We demonstrate that physiological levels of GM1, organized in nanodomains do not seed oligomerization of Aβ40monomers. We show that sphingomyelin triggers oligomerization of Aβ40and that GM1is counteractive thus preventing oligomerization. We propose a molecular explanation that is supported by all-atom molecular dynamics simulations. The preventive role of GM1in the oligomerization of Aβ40suggests that decreasing levels of GM1in the brain, for example, due to aging, could reduce protection against Aβ oligomerization and contribute to the onset of Alzheimer's disease.

Amaro M, Šachl R, Aydogan G, Mikhalyov II, Vácha R, Hof M

IBCH: 3609
Ссылка на статью в журнале: http://doi.wiley.com/10.1002/anie.201603178
Кол-во цитирований на 09.2023: 71
Данные статьи проверены модераторами 2016-01-06