GM1 Ganglioside Inhibits β-Amyloid Oligomerization Induced by Sphingomyelin

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F16%3A00461881" target="_blank" >RIV/61388955:_____/16:00461881 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/anie.201603178" target="_blank" >http://dx.doi.org/10.1002/anie.201603178</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 β-Amyloid Oligomerization Induced by Sphingomyelin

Popis výsledku v původním jazyce

Beta-Amyloid (Aβ) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of Aβ oligomers in vivo. Membrane components sphingomyelin and GM1 have been shown to promote aggregation of Aβ; 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 Aβ40 monomers. We show that sphingomyelin triggers oligomerization of Aβ40 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 Aβ40 suggests that decreasing levels of GM1 in the brain, for example, due to aging, could reduce protection against Aβ oligomerization and contribute to the onset of Alzheimer's disease.

Název v anglickém jazyce

GM1 Ganglioside Inhibits β-Amyloid Oligomerization Induced by Sphingomyelin

Popis výsledku anglicky

Beta-Amyloid (Aβ) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of Aβ oligomers in vivo. Membrane components sphingomyelin and GM1 have been shown to promote aggregation of Aβ; 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 Aβ40 monomers. We show that sphingomyelin triggers oligomerization of Aβ40 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 Aβ40 suggests that decreasing levels of GM1 in the brain, for example, due to aging, could reduce protection against Aβ oligomerization and contribute to the onset of Alzheimer's disease.

Druh

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

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GBP208%2F12%2FG016" target="_blank" >GBP208/12/G016: Řízení struktury a funkce biomolekul na molekulové úrovni: souhra teorie a experimentu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

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

—

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

2-s2.0-84977486670