Kinetic study of Aβ(1-42) amyloidosis in the presence of ganglioside-containing vesicles

[Display omitted] •Monosialogangliosides GM1 could influence the kinetics of Aβ(1-42) fibrillation.•GM1 clusters presented as attachment sites for Aβ(1-42).•Aβ(1-42) fibrils induced by GM1-containing vesicles are toxic to nerve cells. Alzheimer's disease (AD) is characterized by the amyloid-bet...

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Veröffentlicht in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2020-01, Vol.185, p.110615, Article 110615
Hauptverfasser: Dai, Yanping, Zhang, Mingxi, Shi, Xiulei, Wang, Kang, Gao, Guanbin, Shen, Lei, Sun, Taolei
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Sprache:eng
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Zusammenfassung:[Display omitted] •Monosialogangliosides GM1 could influence the kinetics of Aβ(1-42) fibrillation.•GM1 clusters presented as attachment sites for Aβ(1-42).•Aβ(1-42) fibrils induced by GM1-containing vesicles are toxic to nerve cells. Alzheimer's disease (AD) is characterized by the amyloid-beta peptide (Aβ) misfolding to form aberrant amyloid aggregates in the brain. Although recent evidence implicates that amyloid deposition in vivo is highly related to biomembranes, how the characteristic lipid components of neuronal membranes mediate this process remains to be fully elucidated. Herein, we established vesicle models to mimic exosomes and investigated their influence on the kinetics of Aβ(1-42) amyloidosis. By using ternary vesicles composed of three brain lipids monosialoganglioside GM1, cholesterol and sphingomyelin, we found that GM1 could regulate peptide fibrillation by facilitating the conformational transition of Aβ(1-42), and further quantitatively analyzed the influence of GM1-containing vesicles on the kinetics of Aβ(1-42) fibrillation. In addition, GM1-containing vesicles induced the formation of Aβ(1-42) fibrils at low concentrations, and these fibrils were toxic to PC12 cells. By analyzing the role of GM1 in this ternary mixture of membranes at the molecular level, we confirmed that GM1 clusters are presented as attachment sites for peptides, thus promoting the fibrillation of Aβ(1-42).
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2019.110615