Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Neuroscience PhD Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, USA.
J Mol Biol. 2020 Apr 3;432(8):2651-2672. doi: 10.1016/j.jmb.2020.01.037. Epub 2020 Feb 13.
Impaired protein homeostasis and accumulation of damaged or abnormally modified protein are common disease mechanisms in many neurodegenerative disorders, including Parkinson's disease (PD). As one of the major degradation pathways, autophagy plays a pivotal role in maintaining effective turnover of proteins and damaged organelles in cells. Several decades of research efforts led to insights into the potential contribution of impaired autophagy machinery to α-synuclein accumulation and the degeneration of dopaminergic neurons, two major features of PD pathology. In this review, we summarize recent pathological, genetic, and mechanistic findings that link defective autophagy with PD pathogenesis in human patients, animals, and cellular models and discuss current challenges in the field.
蛋白质内稳态受损和受损或异常修饰的蛋白质积累是许多神经退行性疾病（包括帕金森病）的常见疾病机制。自噬作为主要的降解途径之一，在维持细胞内蛋白质和受损细胞器的有效周转中起着关键作用。几十年来的研究工作使人们深入了解了自噬机制受损对α-突触核蛋白积累和多巴胺能神经元退化的潜在贡献，这是帕金森病病理学的两个主要特征。在这篇综述中，我们总结了最近的病理学、遗传学和机制研究发现，这些发现将自噬缺陷与人类患者、动物和细胞模型中的帕金森病发病机制联系起来，并讨论了该领域当前的挑战。
