Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang, China.
Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang, China.
Biomed Pharmacother. 2023 Sep;165:115247. doi: 10.1016/j.biopha.2023.115247. Epub 2023 Jul 27.
Mitochondrial dysfunction, especially in terms of mitochondrial dynamics, has been reported to be closely associated with neuronal outcomes and neurological impairment in cerebral ischemia/hypoxia injury. Dynamin-related protein 1 (Drp1) is a cytoplasmic GTPase that mediates mitochondrial fission and participates in neuronal cell death, calcium signaling, and oxidative stress. The neuroprotective role of Drp1 inhibition has been confirmed in several central nervous system disease models, demonstrating that targeting Drp1 may shed light on novel approaches for the treatment of cerebral ischemia/hypoxia injury. In this review, we aimed to highlight the roles of Drp1 in programmed cell death, oxidative stress, mitophagy, and mitochondrial function to provide a better understanding of mitochondrial disturbances in cerebral ischemia/hypoxia injury, and we also summarize the advances in novel chemical compounds targeting Drp1 to provide new insights into potential therapies for cerebral ischemia/hypoxia injury.
线粒体功能障碍，特别是线粒体动力学方面的障碍，与脑缺血/缺氧损伤中的神经元结局和神经功能障碍密切相关。动力相关蛋白 1（Drp1）是一种细胞质 GTP 酶，介导线粒体分裂，并参与神经元细胞死亡、钙信号和氧化应激。Drp1 抑制在几种中枢神经系统疾病模型中已被证实具有神经保护作用，这表明针对 Drp1 可能为脑缺血/缺氧损伤的治疗提供新的方法。在这篇综述中，我们旨在强调 Drp1 在程序性细胞死亡、氧化应激、线粒体自噬和线粒体功能中的作用，以更好地理解脑缺血/缺氧损伤中的线粒体紊乱，并且我们还总结了针对 Drp1 的新型化学化合物的进展，为脑缺血/缺氧损伤的潜在治疗提供新的见解。
