Belozersky Institute of Physico Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia.
Int J Mol Sci. 2022 Mar 2;23(5):2747. doi: 10.3390/ijms23052747.
The review highlights various aspects of the influence of chaperones on amyloid proteins associated with the development of neurodegenerative diseases and includes studies conducted in our laboratory. Different sections of the article are devoted to the role of chaperones in the pathological transformation of alpha-synuclein and the prion protein. Information about the interaction of the chaperonins GroE and TRiC as well as polymer-based artificial chaperones with amyloidogenic proteins is summarized. Particular attention is paid to the effect of blocking chaperones by misfolded and amyloidogenic proteins. It was noted that the accumulation of functionally inactive chaperones blocked by misfolded proteins might cause the formation of amyloid aggregates and prevent the disassembly of fibrillar structures. Moreover, the blocking of chaperones by various forms of amyloid proteins might lead to pathological changes in the vital activity of cells due to the impaired folding of newly synthesized proteins and their subsequent processing. The final section of the article discusses both the little data on the role of gut microbiota in the propagation of synucleinopathies and prion diseases and the possible involvement of the bacterial chaperone GroE in these processes.
这篇综述重点介绍了伴侣蛋白对与神经退行性疾病发展相关的淀粉样蛋白的影响的各个方面，其中包括我们实验室开展的研究。文章的不同部分专门讨论了伴侣蛋白在α-突触核蛋白和朊病毒蛋白的病理转化中的作用。总结了伴侣素 GroE 和 TRiC 以及基于聚合物的人工伴侣蛋白与淀粉样蛋白形成蛋白相互作用的信息。特别关注了错误折叠和淀粉样蛋白形成蛋白对伴侣蛋白的阻断作用。有人指出，被错误折叠蛋白阻断的功能失活伴侣蛋白的积累可能导致淀粉样聚集的形成，并阻止纤维状结构的解体。此外，由于新合成蛋白质的折叠受损及其随后的加工，各种形式的淀粉样蛋白对伴侣蛋白的阻断可能导致细胞生命活动的病理变化。文章的最后一部分讨论了肠道微生物群在突触核蛋白病和朊病毒病传播中的作用的少量数据，以及细菌伴侣蛋白 GroE 可能参与这些过程。
