Does perturbation in the mitochondrial protein folding pave the way for neurodegeneration diseases?
Does perturbation in the mitochondrial protein folding pave the way for neurodegeneration diseases?
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DOI：
10.1016/j.arr.2019.100997
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发表时间：
2020-01-01
影响因子：
13.1
通讯作者：
Yang, Yang
中科院分区：
文献类型：
--
作者：
Ji, Ting;Zhang, Xiaolu;Yang, Yang
线粒体是广泛存在于真核细胞中的细胞区室，已被证明参与各种合成、代谢和信号传导过程，从而在细胞中发挥重要作用。线粒体未折叠蛋白反应（mtUPR）是当未折叠和错误折叠的蛋白质继续积累时，线粒体逆转向细胞核的信号并维持线粒体蛋白质稳态的反应。多发性神经退行性疾病，包括阿尔茨海默病（AD）、帕金森病（PD）和家族性肌萎缩侧索硬化症（fALS），是公共卫生挑战。每年都有无数的努力试图阐明神经系统疾病的发病机制和治疗，这些疾病在一定程度上与线粒体功能障碍有关。大量研究表明，mtUPR参与并在神经系统疾病的发病机制中发挥重要作用，但其确切机制尚不清楚。进一步研究mtUPR在神经系统疾病中的作用过程，可以帮助我们更准确地了解其发病机制，从而提供新的治疗靶点。本文对秀丽隐杆线虫（Caelihabditis elegans，C. elegans）和哺乳动物的研究，并总结了mtUPR在神经退行性疾病（包括AD、PD和fALS）中的作用。
Mitochondria, which are cell compartments that are widely present in eukaryotic cells, have been shown to be involved in a variety of synthetic, metabolic, and signaling processes, thereby playing a vital role in cells. The mitochondrial unfolded protein response (mtUPR) is a response in which mitochondria reverse the signal to the nucleus and maintain mitochondrial protein homeostasis when unfolded and misfolded proteins continue to accumulate. Multiple neurodegeneration diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and familial amyotrophic lateral sclerosis (fALS), are public health challenges. Every year, countless efforts are expended trying to clarify the pathogenesis and treatment of neurological disorders, which are associated with mitochondrial dysfunction to some extent. Numerous studies have shown that mtUPR is involved in and plays an important role in the pathogenesis of neurological disorders, but the exact mechanism of the disorders is still unclear. Further study of the process of mtUPR in neurological disorders can help us more accurately understand their pathogenesis in order to provide new therapeutic targets. In this paper, we briefly review mtUPR signaling in Caenorhabditis elegans (C. elegans) and mammals and summarize the role of mtUPR in neurodegeneration diseases, including AD, PD and fALS.