再髓鞘化
视神经脊髓炎
神经科学
依达拉奉
多发性硬化
髓鞘
少突胶质细胞
生物
医学
免疫学
药理学
中枢神经系统
作者
Wenjing Luo,Huiming Xu,Li Xu,Wei Jiang,Chen Chen,Yanyu Chang,Chunxin Liu,Zhenming Tian,Xiusheng Qiu,Chichu Xie,Xuejia Li,Haijia Chen,Shuiqing Lai,Long‐Jun Wu,Yifu Cui,Changyong Tang,Wei Qiu
出处
期刊:Glia
[Wiley]
日期:2022-09-12
卷期号:71 (2): 284-304
被引量:10
摘要
Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention. To explore the therapeutic compounds that enhance myelination due to endogenous OPCs, we screened the candidate drugs in mouse neural progenitor cell (NPC)‐derived OPCs. We identified drug edaravone, which is approved by the Food and Drug Administration (FDA), as a promoter of OPC differentiation into mature OLs. Edaravone enhanced remyelination in organotypic slice cultures and in mice, even when edaravone was administered following NMO‐IgG‐induced demyelination, and ameliorated motor impairment in a systemic mouse model of NMOSD. The results of mechanistic studies in NMO‐IgG‐treated mice and the biopsy samples of the brain tissues of NMOSD patients indicated that the mTORC1 signaling pathway was significantly inhibited, and edaravone promoted OPC maturation and remyelination by activating mTORC1 signaling. Furthermore, pharmacological activation of mTORC1 signaling significantly enhanced myelin regeneration in NMOSD. Thus, edaravone is a potential therapeutic agent that promotes lesion repair in NMOSD patients by enhancing OPC maturation.
科研通智能强力驱动
Strongly Powered by AbleSci AI