School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, PR China.
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, PR China.
Colloids Surf B Biointerfaces. 2020 Jan 1;185:110615. doi: 10.1016/j.colsurfb.2019.110615. Epub 2019 Oct 31.
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).
阿尔茨海默病（AD）的特征是淀粉样β肽（Aβ）错误折叠，在大脑中形成异常淀粉样聚集物。尽管最近的证据表明体内淀粉样沉积与生物膜高度相关，但神经元膜的特征脂质成分如何介导这一过程仍有待充分阐明。在此，我们建立了囊泡模型来模拟外泌体，并研究了它们对 Aβ（1-42）淀粉样变性动力学的影响。通过使用由三种脑脂质神经节苷脂 GM1、胆固醇和鞘磷脂组成的三元囊泡，我们发现 GM1 可以通过促进 Aβ（1-42）构象转变来调节肽原纤维形成，并且进一步定量分析了含有 GM1 的囊泡对 Aβ（1-42）原纤维形成动力学的影响。此外，含有 GM1 的囊泡在低浓度下诱导 Aβ（1-42）原纤维的形成，并且这些原纤维对 PC12 细胞有毒性。通过在分子水平上分析 GM1 在这种膜三元混合物中的作用，我们证实 GM1 簇呈现为肽的附着位点，从而促进 Aβ（1-42）的原纤维形成。
