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Updated: Jun 2, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
Research Advances in Chaperone-Mediated Autophagy (CMA) and CMA-Based Protein Degraders
Zhaoping Pan1,2, Xiaowei Huang1, Mingxia Liu1,2
1Department of Dermatology & Venerology, West China Hospital, Sichuan University, Chengdu 610041, China.
Abstract:
Molecular mechanisms of chaperone-mediated autophagy (CMA) constitute essential regulatory elements in cellular homeostasis, encompassing protein quality control, metabolic regulation, cellular signaling cascades, and immunological functions. Perturbations in CMA functionality have been causally associated with various pathological conditions, including neurodegenerative pathologies and neoplastic diseases. Recent advances in targeted protein degradation (TPD) methodologies have demonstrated that engineered degraders incorporating KFERQ-like motifs can facilitate lysosomal translocation and subsequent proteolysis of noncanonical substrates, offering novel therapeutic interventions for both oncological and neurodegenerative disorders. This comprehensive review elucidates the molecular mechanisms, physiological significance, and pathological implications of CMA pathways. Additionally, it provides a critical analysis of contemporary developments in CMA-based degrader technologies, with particular emphasis on their structural determinants, mechanistic principles, and therapeutic applications. The discourse extends to current technical limitations in CMA investigation and identifies key obstacles that must be addressed to advance the development of CMA-targeting therapeutic agents.
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