Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers.
Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers.
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DOI：
10.1021/acs.jpclett.0c01967
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发表时间：
2020-10-01
期刊：
影响因子：
--
通讯作者：
Tobin-Miyaji Y
中科院分区：
文献类型：
--
作者：
Qiang W;Doherty KE;Klees LM;Tobin-Miyaji Y
非纤维状β-淀粉样蛋白（Aβ）寡聚体被认为是阿尔茨海默病（AD）病理学中的主要神经毒性物质。在广泛的模型系统中，Aβ寡聚体的存在可导致膜破裂。然而，这种破坏过程的分子基础仍然未知。我们先前证明，膜掺入的40个残基Aβ（Aβ40）寡聚体可与磷脂形成共聚集体。该过程比Aβ40的纤维化发生得更快，导致更严重的膜破裂。本研究采用固体核磁共振技术，探讨了寡聚体诱导的膜破裂过程中脂质动力学、双层结构和肽-脂质相互作用沿着时间的变化。我们的研究结果表明，磷脂分子进入Aβ40寡聚体核心的C-末端氢键网络存在某些中间状态。这项工作提供了对Aβ40寡聚体诱导的膜破坏的分子机制的见解。
Non-fibrillar β-amyloid (Aβ) oligomers are considered as major neurotoxic species in the pathology of Alzheimer’s disease (AD). The presence of Aβ oligomers were shown to cause membrane disruptions in a broad range of model systems. However, the molecular basis of such disruption process remains unknown. We previously demonstrated that membrane-incorporated 40-residue Aβ (Aβ40) oligomers could form co-aggregates with phospholipids. This process occurred more rapidly than the fibrillization of Aβ40 and led to more severe membrane disruption. The present study probes the time-dependent changes in lipid dynamics, bilayer structures and peptide-lipid interactions along the time course of the oligomer-induced membrane disruption, using the solid-state NMR spectroscopy. Our results suggest the presence of certain intermediate states with phospholipid molecules entering the C-terminal hydrogen-bonding networks of the Aβ40 oligomeric cores. This work provides insights on the molecular mechanisms of Aβ40-oligomer-induced membrane disruption.
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DOI：
10.3233/jad-179941
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cline EN;Bicca MA;Viola KL;Klein WL
通讯作者：
Klein WL
DOI：
10.1016/j.jmr.2015.10.003
发表时间：
2015-12
期刊：
Journal of magnetic resonance (San Diego, Calif. : 1997)
影响因子：
--
作者：
Pandey MK;Zhang R;Hashi K;Ohki S;Nishijima G;Matsumoto S;Noguchi T;Deguchi K;Goto A;Shimizu T;Maeda H;Takahashi M;Yanagisawa Y;Yamazaki T;Iguchi S;Tanaka R;Nemoto T;Miyamoto T;Suematsu H;Saito K;Miki T;Ramamoorthy A;Nishiyama Y
通讯作者：
Nishiyama Y
影响因子：
4.8
作者：
Delgado, Dennis A.;Doherty, Katelynne;Qiang, Wei
通讯作者：
Qiang, Wei
影响因子：
4.8
作者：
Fernández-Pérez EJ;Sepúlveda FJ;Peters C;Bascuñán D;Riffo-Lepe NO;González-Sanmiguel J;Sánchez SA;Peoples RW;Vicente B;Aguayo LG
通讯作者：
Aguayo LG
DOI：
10.1073/pnas.0812033106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Paravastu, Anant K.;Qahwash, Isam;Tycko, Robert
通讯作者：
Tycko, Robert