中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (9): 2437-2453.doi: 10.4103/NRR.NRR-D-24-00432

• 综述:神经损伤修复保护与再生 •    下一篇

急性中枢神经系统损伤中的线粒体自噬:调控机制与治疗潜力

  

  • 出版日期:2025-09-15 发布日期:2024-12-27

Mitophagy in acute central nervous system injuries: regulatory mechanisms and therapeutic potentials

Siyi Xu1, #, Junqiu Jia2, #, Rui Mao3, #, Xiang Cao1, 3, 4, 5, 6, *, Yun Xu1, 2, 3, 4, 5, 6, *   

  1. 1 Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Jiangsu University, Nanjing, Jiangsu Province, China;  2 Department of Neurology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, Jiangsu Province, China;  3 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China; 4 State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu Province, China;  5 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, China;  6 Nanjing Neurology Medical Center, Nanjing, Jiangsu Province, China
  • Online:2025-09-15 Published:2024-12-27
  • Contact: Yun Xu, MD, PhD, xuyun20042001@aliyun.com; Xiang Cao, PhD, caoxiang@njglyy.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81920108017 (to YX), 82130036 (to YX), 82371326 (to XC), 82171310 (to XC); the STI2030-Major Projects, No. 2022ZD0211800 (to YX); and Jiangsu Province Key Medical Discipline, No. ZDXK202216 (to YX).

摘要:

急性中枢神经系统损伤主要包括缺血性卒中、脑出血、蛛网膜下腔出血、外伤性脑损伤和脊髓损伤。在这种情况下,确定最佳治疗方法和改善急性中枢神经系统损伤后患者的长期神经功能至关重要。急性中枢神经系统损伤后,线粒体容易损伤,导致释放有毒的活性氧,从而诱导细胞死亡。线粒体自噬是一种选择形式的自噬,用于消除多余或受损的线粒体。目前,线粒体自噬在急性中枢神经系统损伤中的作用备受关注,但仍需进一步的研究和总结。文章全面讨论了线粒体自噬的过程、分类、相关机制,以及其在各种急性中枢神经系统损伤中的作用和药物治疗的最新进展。文章指出,调节线粒体自噬可能有助于治疗急性中枢神经系统损伤,但过度阻滞或激活线粒体自噬可加重急性中枢神经系统损伤。然而,“过度”线粒体自噬的确切定义尚未明确,并且线粒体自噬在不同的实验模型中的作用可能存在差异,因此关于其在急性中枢神经系统损伤中的益处或危害仍存在争议。未来的研究需要开发更多特异性的线粒体自噬调节剂,以探究其在急性中枢神经系统损伤中的作用。此外,探索线粒体自噬在神经系统中的临床应用也至关重要。

https://orcid.org/0000-0001-5288-0319 (Yun Xu); https://orcid.org/0000-0002-4573-8741 (Xiang Cao)

Abstract: Acute central nervous system injuries, including ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury, are a major global health challenge. Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities. Mitochondria are susceptible to damage after acute central nervous system injury, and this leads to the release of toxic levels of reactive oxygen species, which induce cell death. Mitophagy, a selective form of autophagy, is crucial in eliminating redundant or damaged mitochondria during these events. Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries. In this review, we provide a comprehensive overview of the process, classification, and related mechanisms of mitophagy. We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy. In the final section of this review, we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area

Key words: autophagy,  intracerebral hemorrhage,  ischemic stroke,  mitochondria,  mitochondrial biogenesis,  mitochondrial quality control,   mitophagy,  spinal cord injury,  subarachnoid hemorrhage,  traumatic brain injury