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Chaperone-mediated autophagy and neurodegeneration: connections, mechanisms, and therapeutic implications

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Abstract

Lysosomes degrade dysfunctional intracellular components via three pathways: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Unlike the other two, CMA degrades cytosolic proteins with a recognized KFERQ-like motif in lysosomes and is important for cellular homeostasis. CMA activity declines with age and is altered in neurodegenerative diseases. Its impairment leads to the accumulation of aggregated proteins, some of which may be directly tied to the pathogenic processes of neurodegenerative diseases. Its induction may accelerate the clearance of pathogenic proteins and promote cell survival, representing a potential therapeutic approach for the treatment of neurodegenerative diseases. In this review, we summarize the current findings on how CMA is involved in neurodegenerative diseases, especially in Parkinson’s disease.

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Xiaolei Liu & Beisha Tang

  2. Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Xiaolei Liu, Sihua Huang, Xingqin Wang, Wenming Li & Zixu Mao

  3. Department of Orthopedics, the Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, 710004, China

    Sihua Huang

  4. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

    Xingqin Wang

  5. Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Zixu Mao

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Liu, X., Huang, S., Wang, X. et al. Chaperone-mediated autophagy and neurodegeneration: connections, mechanisms, and therapeutic implications. Neurosci. Bull. 31, 407–415 (2015). https://doi.org/10.1007/s12264-015-1542-8

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