Zhang Ziyan, Miah Mahfuzur, Culbreth Megan, Aschner Michael
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 209, Bronx, NY, 10461, USA.
Neurochem Res. 2016 Feb;41(1-2):409-22. doi: 10.1007/s11064-016-1844-x. Epub 2016 Feb 11.
Autophagy generally refers to cell catabolic and recycling process in which cytoplasmic components are delivered to lysosomes for degradation. During the last two decades, autophagy research has experienced a recent boom because of a newfound connection between this process and many human diseases. Autophagy plays a significant role in maintaining cellular homeostasis and protects cells from varying insults, including misfolded and aggregated proteins and damaged organelles, which is particularly crucial in neuronal survival. Mounting evidence has implicated autophagic dysfunction in the pathogenesis of several major neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease and Huntington's disease, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. In addition, autophagy has also been found to affect neurotoxicity induced by exposure to essential metals, such as manganese, copper, and iron, and other heavy metals, such as cadmium, lead, and methylmercury. This review examines current literature on the role of autophagy in the mechanisms of disease pathogenesis amongst common neurodegenerative disorders and of metal-induced neurotoxicity.
自噬通常是指细胞的分解代谢和再循环过程，在此过程中，细胞质成分被输送到溶酶体进行降解。在过去的二十年里，由于自噬过程与许多人类疾病之间新发现的联系，自噬研究经历了最近的热潮。自噬在维持细胞稳态方面发挥着重要作用，并保护细胞免受各种损伤，包括错误折叠和聚集的蛋白质以及受损的细胞器，这在神经元存活中尤为关键。越来越多的证据表明自噬功能障碍与几种主要神经退行性疾病的发病机制有关，如帕金森病、阿尔茨海默病和亨廷顿病，在这些疾病中，异常和有毒蛋白质聚集体的清除不足会导致细胞应激、功能衰竭和死亡。此外，还发现自噬会影响接触必需金属（如锰、铜和铁）以及其他重金属（如镉、铅和甲基汞）所诱导的神经毒性。本综述考察了关于自噬在常见神经退行性疾病的发病机制以及金属诱导的神经毒性中所起作用的当前文献。
