Molecular chirality mediated amyloid formation on phospholipid surfaces.
Molecular chirality mediated amyloid formation on phospholipid surfaces.
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分子手性介导磷脂表面淀粉样蛋白的形成
DOI：
10.1039/d0sc02212h
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发表时间：
2020-06-25
期刊：
影响因子：
8.4
通讯作者：
Qing G
中科院分区：
文献类型：
--
作者：
Wang X;Wang C;Chu H;Qin H;Wang D;Xu F;Ai X;Quan C;Li G;Qing G
One of the neuropathological features of Alzheimer's disease (AD) is the misfolding of amyloid-β to form amyloid aggregates, a process highly associated with biological membranes. However, how molecular chirality affects the amyloid formation on phospholipid surfaces has seldom been reported. Here, l- and d-aspartic acid-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (l-/d-Asp–DPPE) is synthesized to construct chiral phospholipid bilayers. We discover that the l-Asp–DPPE liposomes slightly inhibit the Aβ(1–40) nucleation process but cannot affect the oligomer elongation process. By contrast, the d-Asp–DPPE liposomes strongly inhibit both nucleation and elongation of the peptide. Notably, l- and d-Asp–DPPE liposomes not only have good biocompatibility but can also rescue Aβ(1–40)-aggregation induced cytotoxicity with significant chiral discrimination, in which the cell viability is higher in the presence of d-Asp–DPPE liposomes. Mechanism analysis and molecular dynamics simulation clearly demonstrate that differential electrostatic interactions of Lys16 in Aβ(1–40) with l- or d-Asp on the phospholipid contribute to the remarkable chiral discrimination. This study provides a deeper understanding of the crucial amyloidosis process from the perspective of the chiral interface and reveals that the convergence of d-amino acids with the liposomes might be a feasible route for AD prevention. A remarkable inhibition effect and chiral discrimination are observed when the amyloid peptide aggregates on chiral phospholipid surfaces.
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影响因子：
5.5
作者：
Inaki M;Sasamura T;Matsuno K
通讯作者：
Matsuno K
影响因子：
2.8
作者：
Grigorashvili, E. I.;Selivanova, O. M.;Galzitskaya, O. V.
通讯作者：
Galzitskaya, O. V.
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
含有神经节苷脂的囊泡存在时 A beta(1-42) 淀粉样变性的动力学研究
影响因子：
5.8
作者：
Dai, Yanping;Zhang, Mingxi;Sun, Taolei
通讯作者：
Sun, Taolei
影响因子：
14.8
作者：
Greenfield, Norma J.
通讯作者：
Greenfield, Norma J.