Targeting chaperone-mediated autophagy in neurodegenerative diseases:mechanisms and therapeutic potential  

作　　者：Jin Wu Wan Xu Ying Su Guang-hui Wang Jing-jing Ma 

机构地区：[1]Department of Pharmacy,The Fourth Affiliated Hospital of Soochow University,Suzhou Dushu Lake Hospital,Medical Center of Soochow University,Suzhou,215123,China [2]Laboratory of Molecular Neuropathology,Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences,Soochow University,Suzhou,215123,China

出　　处：《Acta Pharmacologica Sinica》2025年第4期816-828,共13页中国药理学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(grants 32400789 and 32070970);the Natural Science Foundation of Jiangsu Province(grants BK20240436);the Suzhou Science and Technology Development Plan(SZM2023006 and SKYD2023179);the Gusu Key Health Talent Program of Suzhou(GSWS2022122).

摘　　要：The pathological hallmarks of various neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease prominently feature the accumulation of misfolded proteins and neuroinflammation.Chaperone-mediated autophagy(CMA)has emerged as a distinct autophagic process that coordinates the lysosomal degradation of specific proteins bearing the pentapeptide motif Lys-Phe-Glu-Arg-Gln(KFERQ),a recognition target for the cytosolic chaperone HSC70.Beyond its role in protein quality control,recent research underscores the intimate interplay between CMA and immune regulation in neurodegeneration.In this review,we illuminate the molecular mechanisms and regulatory pathways governing CMA.We further discuss the potential roles of CMA in maintaining neuronal proteostasis and modulating neuroinflammation mediated by glial cells.Finally,we summarize the recent advancements in CMA modulators,emphasizing the significance of activating CMA for the therapeutic intervention in neurodegenerative diseases.

关 键 词：neurodegenerative diseases chaperone-mediated autophagy neuronal proteostasis NEUROINFLAMMATION CMA modulators 

分 类 号：R741[医药卫生—神经病学与精神病学]