Zheng Shuangshuang, Zhao Jingwei
Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Zhejiang University School of Medicine, Hangzhou 310058, China.
Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 Aug 25;49(4):524-530. doi: 10.3785/j.issn.1008-9292.2020.08.12.
Failure to remyelinate and rewrap the demyelinated axons has been revealed as the major hurdle for treatment of multiple sclerosis (MS), and the bottleneck is the inability of oligodendrocyte progenitor cell (OPC) to differentiate into mature oligodendrocyte. Remyelination is a spontaneous regenerative process, which includes activation, migration and differentiation of OPC, and is believed to protect the axon and further halt neurodegeneration. In recent years, studies have identified many potential drug targets for efficiently promoting OPC differentiation in demyelination models, such as metformin, clemostine, and drug targets as myelin transcription factor 1-like protein (Myt1L), N-methyl-D-aspartic acid (NMDA) receptor, connexin 43 (Cx43), G protein coupled receptor 17 (GPR17), κ opioid receptor (KOR), sterol 14α-demethylase (CYP51), Δ14-sterol reductase (TM7SF2), emopamil-binding protein (EBP). This review summarizes the recent progress on the mechanisms underlying the activation, migration and differentiation of OPC in remyelination with special focus on studies using demyelination models of MS, which may provide insights of further exploring new therapeutic strategies for MS.
未能对脱髓鞘轴突进行重新髓鞘化和重新包裹已被揭示为治疗多发性硬化症（MS）的主要障碍，而瓶颈在于少突胶质前体细胞（OPC）无法分化为成熟的少突胶质细胞。重新髓鞘化是一个自发的再生过程，包括OPC的激活、迁移和分化，被认为可以保护轴突并进一步阻止神经退行性变。近年来，研究已经确定了许多在脱髓鞘模型中有效促进OPC分化的潜在药物靶点，如二甲双胍、氯马斯汀，以及作为髓磷脂转录因子1样蛋白（Myt1L）、N-甲基-D-天冬氨酸（NMDA）受体、连接蛋白43（Cx43）、G蛋白偶联受体17（GPR17）、κ阿片受体（KOR）、甾醇14α-脱甲基酶（CYP51）、Δ14-甾醇还原酶（TM7SF2）、埃莫帕米结合蛋白（EBP）的药物靶点。本文综述了近期关于重新髓鞘化过程中OPC激活、迁移和分化机制的研究进展，特别关注使用MS脱髓鞘模型的研究，这可能为进一步探索MS的新治疗策略提供见解。
