中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (8): 1660-1670.doi: 10.4103/1673-5374.389361

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

中枢神经系统损伤中的自噬、焦亡、铁死亡和程序性坏死间的相互作用

  

  • 出版日期:2024-08-15 发布日期:2024-01-03

Crosstalk among mitophagy, pyroptosis, ferroptosis, and necroptosis in central nervous system injuries

Li Zhang, Zhigang Hu, Zhenxing Li, Yixing Lin*   

  1. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China
  • Online:2024-08-15 Published:2024-01-03
  • Contact: Yixing Lin, MD, lyx2022nj@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82101461 (to ZL).

摘要:

目前缺乏有效的方法治疗中枢神经系统损伤。程序性细胞死亡是一种具有多种类型的主动、有序的细胞死亡形式,由于其在决定细胞命运方面的作用,近年来引起了研究者的极大关注。越来越多的研究表明,包括线粒体自噬、焦亡、铁死亡和程序性坏死在内的程序性细胞死亡参与了中枢神经系统损伤,并在脑损伤的进展中发挥了重要作用。但是,这个主题还有待更新和总结。文章总结了在中枢神经系统损伤中,线粒体自噬、焦亡、铁死亡和程序性坏死之间的相互作用可以抑制炎症、氧化应激和细胞死亡。此外,已经发现线粒体自噬的多种上游分子,如SIRT3、FOXO3a、PGAM5和AMPK,可靶向CNS损伤中的焦亡和程序性坏死。因此,程序性细胞死亡之间的相互作用可作为中枢神经系统损伤的潜在靶点。程序性细胞死亡之间相互作用的微阵列、蛋白质组学和代谢组学分析可为神经元功能的恢复和脑损伤的治疗提供新的途径。因此,对程序性细胞死亡的进一步研究将为探索中枢神经系统损伤的发病机制开辟更广阔的领域,并为中枢神经系统损伤提供更好的临床治疗方法。

https://orcid.org/0000-0002-9927-8277 (Yixing Lin)

Abstract: Central nervous system injuries have a high rate of resulting in disability and mortality; however, at present, effective treatments are lacking. Programmed cell death, which is a genetically determined form of active and ordered cell death with many types, has recently attracted increasing attention due to its functions in determining the fate of cell survival. A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage. In this review, we provide an overview of the role of programmed cell death in central nervous system injuries, including the pathways involved in mitophagy, pyroptosis, ferroptosis, and necroptosis, and the underlying mechanisms by which mitophagy regulates pyroptosis, ferroptosis, and necroptosis. We also discuss the new direction of therapeutic strategies targeting mitophagy for the treatment of central nervous system injuries, with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury. In conclusion, based on these properties and effects, interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

Key words: central nervous system injuries, death pyroptosis, ferroptosis, inflammation, mitophagy, necroptosis, programmed cell