(GM1) Ganglioside Inhibits beta-Amyloid Oligomerization Induced bySphingomyelin

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F16%3A00088531" target="_blank" >RIV/00216224:14740/16:00088531 - isvavai.cz</a>

Výsledek na webu

<a href="http://onlinelibrary.wiley.com/doi/10.1002/anie.201603178/abstract" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/anie.201603178/abstract</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.201603178" target="_blank" >10.1002/anie.201603178</a>

Jazyk výsledku

angličtina

Název v původním jazyce

(GM1) Ganglioside Inhibits beta-Amyloid Oligomerization Induced bySphingomyelin

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

(GM1) Ganglioside Inhibits beta-Amyloid Oligomerization Induced bySphingomyelin

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Angewandte Chemie International Edition

ISSN

1433-7851

e-ISSN

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Svazek periodika

55

Číslo periodika v rámci svazku

32

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

5

Strana od-do

9411-9415

Kód UT WoS článku

000383371800055

EID výsledku v databázi Scopus

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