[关键词]
[摘要]
线粒体稳态失衡在脑缺血/再灌注损伤(cerebral ischemia/reperfusion injury,CI/RI)病理过程中扮演重要角色。线粒体分裂/融合的动态调节(线粒体动力学)作为线粒体质量控制(mitochondrial quality control,MQC)的关键环节,在CI/RI中维持线粒体稳态发挥重要作用。小泛素相关修饰物(small ubiquitin-related modifier,SUMO)修饰是一类存在于细胞内动态可逆的蛋白质翻译后修饰形式,通过对底物蛋白进行多步酶促反应以完成对靶蛋白的SUMO修饰和去SUMO修饰过程,进而影响底物蛋白的亚细胞定位、蛋白互作和稳定性,其普遍参与了蛋白转运、信号传导、DNA修复、炎症反应及氧化应激等病理生理过程。线粒体动力学及相关蛋白通过SUMO化修饰调控线粒体融合和分裂,进而调节线粒体稳态,在CI/RI进展与转归中发挥着关键作用。中药在防治缺血性脑病方面具有明显优势,综述了线粒体分裂/融合过程中相关蛋白的SUMO化修饰的调节机制,以及靶向调节线粒体动力学及相关蛋白SUMO化修饰防治CI/RI的中医药研究进展,以期为缺血性脑病如卒中的康复治疗提供新的治疗策略与潜在药用靶点。
[Key word]
[Abstract]
Imbalance in mitochondrial homeostasis plays an important role in the pathological process of cerebral ischemia/reperfusion injury (CI/RI). Dynamic regulation of mitochondrial fission/fusion (mitochondrial dynamics), as a key part of mitochondrial quality control (MQC), plays a crucial role in maintaining mitochondrial homeostasis in CI/RI. Small ubiquitin-related modifier (SUMO) is a kind of dynamic and reversible post-translational modification of proteins in cells. SUMOylation and deSUMOylation of target proteins are completed through multi-step enzymatic reactions of substrate proteins, thus affecting subcellular localization, protein interaction and stability of substrate proteins. It is generally involved in pathophysiological processes such as protein transport, signal transduction, DNA repair, inflammatory response and oxidative stress. Mitochondrial dynamics and related proteins regulate mitochondrial fission and fusion through SUMOylation to regulate mitochondrial homeostasis and effect the progression and prognosis of CI/RI. Traditional Chinese medicine has obvious advantages in preventing and treating ischemic encephalopathy. In this paper, we reviewed the regulatory mechanism of SUMOylation of proteins involved in mitochondrial fission/fusion, as well as the research progress of traditional Chinese medicine targeted mitochondrial dynamics and SUMOylation of related proteins in treating CI/RI, in order to provide new therapeutic strategies and potential therapeutic targets for the treatment and rehabilitation for ischemic encephalopathy especially ischemic stroke.
[中图分类号]
[基金项目]
国家自然科学基金资助项目(82174167);湖南省自然科学基金面上项目(2021JJ30499);湖南省国内一流培育学科中西医结合开放基金项目(2020ZXYJH63);湖南中医药大学研究生科研创新项目(2021CX63)