Department of Anatomy, College of Medicine, Inha University, Incheon 22212, Korea.
Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Korea.
Int J Mol Sci. 2020 May 10;21(9):3369. doi: 10.3390/ijms21093369.
Cells have developed elaborate quality-control mechanisms for proteins and organelles to maintain cellular homeostasis. Such quality-control mechanisms are maintained by conformational folding via molecular chaperones and by degradation through the ubiquitin-proteasome or autophagy-lysosome system. Accumulating evidence suggests that impaired autophagy contributes to the accumulation of intracellular inclusion bodies consisting of misfolded proteins, which is a hallmark of most neurodegenerative diseases. In addition, genetic mutations in core autophagy-related genes have been reported to be linked to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Conversely, the pathogenic proteins, such as amyloid β and α-synuclein, are detrimental to the autophagy pathway. Here, we review the recent advances in understanding the relationship between autophagic defects and the pathogenesis of neurodegenerative diseases and suggest autophagy induction as a promising strategy for the treatment of these conditions.
细胞已经进化出复杂的质量控制机制来维持蛋白质和细胞器的细胞内平衡。这种质量控制机制是通过分子伴侣的构象折叠和通过泛素-蛋白酶体或自噬溶酶体系统的降解来维持的。越来越多的证据表明，自噬功能受损会导致包含错误折叠蛋白质的细胞内包涵体的积累，这是大多数神经退行性疾病的一个标志。此外，核心自噬相关基因的遗传突变已被报道与神经退行性疾病有关，如阿尔茨海默病、帕金森病和亨廷顿病。相反，致病性蛋白质，如淀粉样β和α-突触核蛋白，对自噬途径有害。在这里，我们综述了理解自噬缺陷与神经退行性疾病发病机制之间关系的最新进展，并提出诱导自噬作为治疗这些疾病的一种有前途的策略。
