Publication details
(GM1) Ganglioside Inhibits beta-Amyloid Oligomerization Induced bySphingomyelin
| Authors | |
|---|---|
| Year of publication | 2016 |
| Type | Article in Periodical |
| Magazine / Source | Angewandte Chemie International Edition |
| MU Faculty or unit | |
| 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. |
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