(GM1) Ganglioside Inhibits beta-Amyloid Oligomerization Induced bySphingomyelin

Investor logo
Investor logo
Investor logo

Warning

This publication doesn't include Institute of Computer Science. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
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:

You are running an old browser version. We recommend updating your browser to its latest version.

More info