(GM1) Ganglioside Inhibits beta-Amyloid Oligomerization Induced bySphingomyelin

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Authors	AMARO Mariana ŠACHL Radek AYDOGAN Gokcan MIKHALYOV Ilya I. VÁCHA Robert HOF Martin
Year of publication	2016
Type	Article in Periodical
Magazine / Source	Angewandte Chemie International Edition
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://onlinelibrary.wiley.com/doi/10.1002/anie.201603178/abstract
Doi	http://dx.doi.org/10.1002/anie.201603178
Field	Biochemistry
Keywords	Alzheimer's disease; amyloid beta-peptides; diffusion coefficients; fluorescence spectroscopy; neuroprotectives
Description	beta-Amyloid (A beta) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of A beta oligomers in vivo. Membrane components sphingomyelin and GM(1) have been shown to promote aggregation of A beta; however, these studies were performed under extreme, non-physiological conditions. We demonstrate that physiological levels of GM(1), organized in nanodomains do not seed oligomerization of A beta(40) monomers. We show that sphingomyelin triggers oligomerization of A beta(40) and that GM(1) is counteractive thus preventing oligomerization. We propose a molecular explanation that is supported by all-atom molecular dynamics simulations. The preventive role of GM(1) in the oligomerization of A beta(40) suggests that decreasing levels of GM(1) in the brain, for example, due to aging, could reduce protection against A beta oligomerization and contribute to the onset of Alzheimer's disease.
Related projects:	CERIT Scientific Cloud CEITEC - Central European Institute of Technology Self-assembly of amphiphilic peptides with helical character Velká infrastruktura CESNET