神经退行性疾病蛋白纤维化及其与界面的手性相互作用

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神经退行性疾病蛋白纤维化及其与界面的手性相互作用

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- 神经退行性疾病蛋白纤维化及其与界面的手性相互作用
- Protein Fibrillation in Neurodegenerative Diseases and Its Chiral Interaction with Interfaces
- 高分子学报 2019年50卷第6期页码：575-587
- 作者机构：
  
  1. 武汉理工大学化学化工与生命科学学院
  2. 材料复合新技术国家重点实验室　武汉 430070
- 作者简介：
  
  E-mail: leishen@whut.edu.cn Lei Shen, Email: leishen@whut.edu.cn
  E-mail: suntl@whut.edu.cn Taolei Sun, Email:suntl@whut.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 21574051)资助项目()
- DOI：10.11777/j.issn1000-3304.2019.18276
  中图分类号：
- 纸质出版日期：2019-6，
  
  网络出版日期：2019-3-1，
  
  收稿日期：2018-12-27，
  
  修回日期：2019-1-22，
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殷强, 刘晶晶, 田梦婷, 谢浩, 沈雷, 孙涛垒. 神经退行性疾病蛋白纤维化及其与界面的手性相互作用[J]. 高分子学报, 2019,50(6):575-587.

Qiang Yin, Jing-jing Liu, Meng-ting Tian, Hao Xie, Lei Shen, Tao-lei Sun. Protein Fibrillation in Neurodegenerative Diseases and Its Chiral Interaction with Interfaces[J]. Acta Polymerica Sinica, 2019,50(6):575-587.
殷强, 刘晶晶, 田梦婷, 谢浩, 沈雷, 孙涛垒. 神经退行性疾病蛋白纤维化及其与界面的手性相互作用[J]. 高分子学报, 2019,50(6):575-587. DOI： 10.11777/j.issn1000-3304.2019.18276.

Qiang Yin, Jing-jing Liu, Meng-ting Tian, Hao Xie, Lei Shen, Tao-lei Sun. Protein Fibrillation in Neurodegenerative Diseases and Its Chiral Interaction with Interfaces[J]. Acta Polymerica Sinica, 2019,50(6):575-587. DOI： 10.11777/j.issn1000-3304.2019.18276.

摘要

神经退行性疾病(neurodegenerative diseases，NDs)的标志性病理特征是相关蛋白的错误折叠、聚集并纤维化，即淀粉样变性. 细胞膜界面在NDs病理过程中扮演了重要角色，这些过程包括NDs蛋白的产生、淀粉样单元的细胞内扩散、细胞间传播、细胞内吞及脑内清除. 因此，NDs蛋白与磷脂膜界面的相互作用显著影响蛋白纤维化和NDs病理过程. 手性是磷脂膜的基本化学属性，不同手性特征能产生不同生物物理效应. 因此，磷脂膜界面的手性特征会显著影响NDs蛋白纤维化以及NDs病理过程. 本文揭示了界面在NDs蛋白纤维化和NDs病理过程中的重要性，从分子水平重点阐述了界面的手性特征对NDs蛋白纤维化的影响，探讨了基于手性相互作用的NDs药物设计方法，有助于深入理解NDs病理机制，并对开发能够治愈NDs的药物具有重要意义.

Abstract

A hallmark event of neurodegenerative diseases (NDs) is the misfolding

aggregation and fibrillation of related proteins

namely amyloidosis. For example

amyloid-

β

(A

β

) and Tau

α

-synuclein (

α

-syn)

superoxide dismutase 1 (SOD1) and huntingtin exon 1 (HTTexon1) are tightly linked to Alzheimer’s Disease (AD)

Parkinson Disease (PD)

Amyotrophic Lateral Sclerosis (ALS) and Huntington ’s Disease (HD)

respectively. Plasma membrane plays a crucial role in the pathological processes of NDs

including the production

intracellular diffusion

intercellular transmission

endocytosis and clearance of NDs proteins and the resulting aggregates. Therefore

the interactions between NDs proteins and membrane interfaces significantly influence the protein fibrillation and NDs pathogenesis. Properties of membrane interfaces including amphiphilicity and charge density can influence the adsorption of proteins onto membranes and thus the protein folding and aggregation. As the basic chemical property of plasma membranes

chirality can determine key biophysical interactions. The alternation of molecule chirality can cause entirely different biophysical interactions and thus the biofunctions. From this biomimetic perspective

extensive works have demonstrated that the chirality of interfaces can significantly affect protein-surface interactions and thus the fibrillation processes. This brings us to reconsider the stereoselective interactions between NDs proteins and the chiral moieties on membrane interfaces and their impact during NDs pathogenesis. This review article is aimed to reveal the key role of membrane interfaces in protein fibrillation and discuss the impact of interfaces during NDs pathogenesis. The stereoselective protein-membrane interactions and their effects on protein fibrillation are elucidated from a molecular level. The designs of NDs drugs based on chiral interactions are also discussed. These specific aims will deepen our mechanistic insights into how interfaces affect NDs pathogenesis and facilitate the discovery of effective drugs for preventing protein fibrillation and eventually the cure of NDs.

关键词

神经退行性疾病蛋白纤维化界面手性

Keywords

Neurodegenerative diseasesProtein fibrillationInterfaceChirality

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