Cheng Biao, Li Yang, Ma Liang, Wang Zhuoyi, Petersen Robert B, Zheng Ling, Chen Yuchen, Huang Kun
Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430023, China; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430023, China.
Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Biochim Biophys Acta Biomembr. 2018 Sep;1860(9):1876-1888. doi: 10.1016/j.bbamem.2018.02.013. Epub 2018 Feb 18.
The toxic deposition of misfolded amyloidogenic proteins is associated with more than fifty protein misfolding diseases (PMDs), including Alzheimer's disease, Parkinson's disease and type 2 diabetes mellitus. Protein deposition is a multi-step process modulated by a variety of factors, in particular by membrane-protein interaction. The interaction results in permeabilization of biomembranes contributing to the cytotoxicity that leads to PMDs. Different biological and physiochemical factors, such as protein sequence, lipid composition, and chaperones, are known to affect the membrane-protein interaction. Here, we provide a comprehensive review of the mechanisms and contributing factors of the interaction between biomembranes and amyloidogenic proteins, and a summary of the therapeutic approaches to PMDs that target this interaction. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.
错误折叠的淀粉样蛋白的毒性沉积与五十多种蛋白质错误折叠疾病(PMD)相关,包括阿尔茨海默病、帕金森病和2型糖尿病。蛋白质沉积是一个由多种因素调节的多步骤过程,特别是通过膜-蛋白质相互作用。这种相互作用导致生物膜通透性增加,从而导致细胞毒性,进而引发PMD。已知不同的生物和物理化学因素,如蛋白质序列、脂质组成和伴侣蛋白,会影响膜-蛋白质相互作用。在此,我们全面综述了生物膜与淀粉样蛋白相互作用的机制和影响因素,并总结了针对这种相互作用的PMD治疗方法。本文是由阿亚卢萨米·拉马穆尔蒂编辑的名为《细胞膜界面的蛋白质聚集和错误折叠》特刊的一部分。