Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (6): 2110-2124.doi: 10.4103/NRR.NRR-D-24-01467

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The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies

Rui Wang1, 2, #, Zhen Niu3, #, Runze Tian1, 3, #, Aini Chen1, 2, Huangmei Liao1, 3, Rui Kuang1 , Ying Feng3 , Guangyu Chin4 , Jiesheng Xie1 , Ping Zhu1, 3, 5, *, Chi Teng Vong6, 7, *, Ge Li1, 2, 3, 5, *   

  1. 1 Guangdong Provincial Key Laboratory of Pathogenesis, Targeted Prevention and Treatment of Heart Disease, Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China;  2 School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China;  3 School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China;  4 Sub-specialty Diagnosis Research Center of Neurological Disorder, Guangzhou Huayin Medical Laboratory Center, Guangzhou, Guangdong Province, China;  5 Guangzhou Key Laboratory of Cardiac Pathogenesis and Prevention, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China;  6 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region, China;  7 Macau Center for Research and Development in Chinese Medicine, University of Macau, Macao Special Administrative Region, China
  • Online:2026-06-15 Published:2025-09-18
  • Contact: Ge Li, MD, PhD, lige@gdph.org.cn; Chi Teng Vong, PhD, gigictvong@um.edu.mo; Ping Zhu, PhD, tanganqier@163.com.
  • Supported by:
    This work was funded by the National Natural Science Foundation of China, No. 82271395 (to GL); the Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515030073 (to GL); the grants from University of Macau Research Committee, China, No. MYRG2022-00074-ICMS (to CTV); Guangzhou Science and Technology Program Project, No. 2025A04J4740 (to GL).

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Abstract: Spinal cord injury is a neurological disorder resulting from trauma, typically affecting sensory and motor function at the injury site, even leading to paralysis and internal dysfunction. The treatment of spinal cord injury mainly relies on pharmacological and surgical interventions; however, significant challenges remain in the protection and repair of neural tissues. Autophagy, an intracellular process responsible for the degradation and recycling of macromolecular components, plays a vital role in spinal cord injury, alleviating the severity of injury by inhibiting cell apoptosis and inflammatory responses. In this review, we provide an overview of the physiological mechanisms underlying autophagy and spinal cord injury and detail the crosstalk between autophagy and other modes of cell death in spinal cord injury. In addition, we discuss the potential of targeting autophagy as a therapeutic strategy for spinal cord injury through approaches that focus on promoting or inhibiting this process, targeting specific autophagic substrates or pathways, and combining autophagy modulation with other neuroprotective or restorative interventions. In summary, this review proposes that strict regulation of autophagy may represent a viable strategy for the treatment of spinal cord injury.

Key words: apoptosis, autophagy, chaperone-mediated autophagy, ferroptosis, macroautophagy, microautophagy, neuronal protection, parthanatos, pyroptosis, spinal cord injury