Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (1): 6-20.doi: 10.4103/NRR.NRR-D-23-00995

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

Xiu-Yun Zhao1, 2, De-En Xu3, Ming-Lei Wu1, 2, Ji-Chuan Liu1, 2, Zi-Ling Shi1, 2, Quan-Hong Ma1, 2, *   

  1. 1Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; 2Institute of Neuroscience & Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University, Suzhou, Jiangsu Province, China; 3Department of Neurology, Jiangnan University Medical Center, Wuxi, Jiangsu Province, China
  • Online:2025-01-15 Published:2025-01-15
  • Contact: Quan-Hong Ma, PhD, maquanhong@suda.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 92049120 and 81870897; STI2030-Major Projects, No. 2021ZD0204001; Guangdong Key Project for Development of New Tools for the Diagnosis and Treatment of Autism, No. 2018B030335001; the Natural Science Foundation of Jiangsu Province, No. BK20181436; the National Major Scientific and Technological Special Project for Significant New Drug Development, No. 2019ZX09301102; the Discipline Construction Program of the Second Affiliated Hospital of Soochow University, No. XKTJ-TD202003; Sino-German Cooperation Mobility Programme, No. M-0679; the Science and Technology Project of Suzhou, No. SKY2022161; and Research Project of Neurological Diseases of the Second Affiliated Hospital of Soochow University Medical Center, No. ND2023A01 (all to QHM).

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Abstract: The endoplasmic reticulum, a key cellular organelle, regulates a wide variety of cellular activities. Endoplasmic reticulum autophagy, one of the quality control systems of the endoplasmic reticulum, plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover, remodeling, and proteostasis. In this review, we briefly describe the endoplasmic reticulum quality control system, and subsequently focus on the role of endoplasmic reticulum autophagy, emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements. We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases. In summary, this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders. This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

Key words: autophagy, endoplasmic reticulum, endoplasmic reticulum autophagy, endoplasmic reticulum quality control system, endoplasmic reticulum receptors, endoplasmic reticulum-associated degradation, neurodegeneration, neurodegenerative disease, selective autophagy, unfolded protein response