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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Angew+Chem+Int+Ed+Engl 2016 ; 55 (32): 9411-5 Nephropedia Template TP
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GM1 Ganglioside Inhibits ??Amyloid Oligomerization Induced by Sphingomyelin #MMPMID27295499
Amaro M; ?achl R; Aydogan G; Mikhalyov II; Vácha R; Hof M
Angew Chem Int Ed Engl 2016[Aug]; 55 (32): 9411-5 PMID27295499show ga
??Amyloid (A?) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of A? oligomers in vivo. Membrane components sphingomyelin and GM1 have been shown to promote aggregation of A?; 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 A?40 monomers. We show that sphingomyelin triggers oligomerization of A?40 and that GM1 is counteractive thus preventing oligomerization. We propose a molecular explanation that is supported by all?atom molecular dynamics simulations. The preventive role of GM1 in the oligomerization of A?40 suggests that decreasing levels of GM1 in the brain, for example, due to aging, could reduce protection against A? oligomerization and contribute to the onset of Alzheimer's disease.