Ma Liang, Li Xi, Petersen Robert B, Peng Anlin, Huang Kun
Department of Pharmacy, Wuhan Mental Health Center, Wuhan, China; Department of Pharmacy, Wuhan Hospital for Psychotherapy, Wuhan, China.
Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biophys Chem. 2023 May;296:106984. doi: 10.1016/j.bpc.2023.106984. Epub 2023 Feb 26.
Protein misfolding diseases (PMDs) in humans are characterized by the deposition of protein aggregates in tissues, including Alzheimer's disease, Parkinson's disease, type 2 diabetes, and amyotrophic lateral sclerosis. Misfolding and aggregation of amyloidogenic proteins play a central role in the onset and progression of PMDs, and these processes are regulated by multiple factors, especially the interaction between proteins and bio-membranes. Bio-membranes induce conformational changes in amyloidogenic proteins and affect their aggregation; on the other hand, the aggregates of amyloidogenic proteins may cause membrane damage or dysfunction leading to cytotoxicity. In this review, we summarize the factors that affect the binding of amyloidogenic proteins and membranes, the effects of bio-membranes on the aggregation of amyloidogenic proteins, mechanisms of membrane disruption by amyloidogenic aggregates, technical approaches for detecting these interactions, and finally therapeutic strategies targeting membrane damage caused by amyloidogenic proteins.
人类的蛋白质错误折叠疾病(PMD)的特征是蛋白质聚集体在组织中沉积,包括阿尔茨海默病、帕金森病、2型糖尿病和肌萎缩侧索硬化症。淀粉样蛋白的错误折叠和聚集在PMD的发病和进展中起核心作用,这些过程受多种因素调节,尤其是蛋白质与生物膜之间的相互作用。生物膜诱导淀粉样蛋白的构象变化并影响其聚集;另一方面,淀粉样蛋白的聚集体可能导致膜损伤或功能障碍,从而导致细胞毒性。在这篇综述中,我们总结了影响淀粉样蛋白与膜结合的因素、生物膜对淀粉样蛋白聚集的影响、淀粉样聚集体破坏膜的机制、检测这些相互作用的技术方法,以及最后针对淀粉样蛋白引起的膜损伤的治疗策略。