Li Wenming, Dou Juan, Yang Jing, Xu Haidong, She Hua
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Curr Pharmacol Rep. 2018 Jun;4(3):261-275. doi: 10.1007/s40495-018-0138-1. Epub 2018 May 2.
To reason that targeting chaperone-mediated autophagy (CMA) represents a promising approach for disease therapy, we will summarize advances in researches on the relationship between CMA and diseases and discuss relevant strategies for disease therapy by targeting the CMA process.
CMA is a unique kind of selective autophagy in lysosomes. Under physiological conditions, CMA participates in the maintenance of cellular homeostasis by protein quality control, bioenergetics, and timely regulated specific substrate-associated cellular processes. Under pathological conditions, CMA interplays with various disease conditions. CMA makes adaptive machinery to address stress, while disease-associated proteins alter CMA which is involved in pathogeneses of diseases. As more proteins are identified as CMA substrates and regulators, dysregulation of CMA has been implicated in an increasing number of diseases, while rectifying CMA alteration may be a benefit for these diseases.
Alterations of CMA in diseases mainly including neurodegenerative diseases and many cancers raise the possibility of targeting CMA to recover cellular homeostasis as one potential strategy for therapy of relevant diseases.
为了论证靶向伴侣介导的自噬（CMA）是一种很有前景的疾病治疗方法，我们将总结CMA与疾病关系的研究进展，并讨论通过靶向CMA过程进行疾病治疗的相关策略。
CMA是溶酶体中一种独特的选择性自噬。在生理条件下，CMA通过蛋白质质量控制、生物能量学以及及时调节特定底物相关的细胞过程参与细胞稳态的维持。在病理条件下，CMA与各种疾病状态相互作用。CMA形成适应性机制以应对应激，而疾病相关蛋白会改变CMA，后者参与疾病的发病过程。随着越来越多的蛋白质被鉴定为CMA底物和调节因子，CMA的失调与越来越多的疾病有关，而纠正CMA改变可能对这些疾病有益。
CMA在包括神经退行性疾病和许多癌症在内的疾病中的改变，增加了靶向CMA以恢复细胞稳态作为相关疾病治疗的一种潜在策略的可能性。
