Chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapy

Chaperone-mediated autophagy (CMA) is the selective degradation process of intracellular components by lysosomes, which is required for the degradation of aggregate-prone proteins and contributes to proteostasis maintenance. Proteostasis is essential for normal cell function and survival, and it is determined by the balance of protein synthesis and degradation. Because postmitotic neurons are highly susceptible to proteostasis disruption, CMA is vital for the nervous system. Since Parkinson's disease (PD) was first linked to CMA dysfunction, an increasing number of studies have shown that CMA loss, as seen during aging, occurs in the pathogenetic process of neurodegenerative diseases. Here, we review the molecular mechanisms of CMA, as well as the physiological function and regulation of this autophagy pathway. Following, we highlight its potential role in neurodegenerative diseases, and the latest advances and challenges in targeting CMA in therapy of neurodegenerative diseases.

Automated summary

Chaperone-mediated autophagy (CMA) is a crucial process for the selective degradation of intracellular components, particularly aggregate-prone proteins, and is involved in the maintenance of proteostasis. Disruption of proteostasis, which refers to the balance between protein synthesis and degradation, can lead to neurodegenerative diseases, especially in postmitotic neurons. Studies have shown that CMA dysfunction, similar to aging, plays a role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease. This review focuses on the molecular mechanisms, physiological function, and regulation of CMA, as well as its potential role and recent advances in the therapy of neurodegenerative diseases.