@article{e4efe839a6a4418ebabe952bb25b4603,
title = "Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation",
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.",
keywords = "edaravone, mTORC1, neuromyelitis optica spectrum disorder, oligodendrocyte progenitor cells, remyelination",
author = "Wenjing Luo and Huiming Xu and Li Xu and Wei Jiang and Chen Chen and Yanyu Chang and Chunxin Liu and Zhenming Tian and Xiusheng Qiu and Chichu Xie and Xuejia Li and Haijia Chen and Shuiqing Lai and Longjun Wu and Yaxiong Cui and Changyong Tang and Wei Qiu",
note = "Funding Information: National Key research and development Program of China, Grant/Award Number: 2022ZD0214300; National Natural Science Foundation of China, Grant/Award Numbers: 32100787, 81771300, 81971140; Natural Science Foundation of Guangdong Province, Grant/Award Number: 2020A1515010053 Funding information Funding Information: The authors would like to thank Prof. Yoichiro Abe and colleagues from Keio University for their generous gift of monoclonal AQP4-IgG. We thank Zhengqi Lu, Xiaoyan Han, Lisheng Peng, Xiaofen Zhong, and Haixia Wang for their valuable assistance with experimental techniques. This research was supported by grants from the National Natural Science Foundation of China (81771300, 81971140, and 32100787), the National Key R&D Program of China (2022ZD0214300), and the Natural Science Foundation of Guangdong Province (2020A1515010053). Funding Information: The authors would like to thank Prof. Yoichiro Abe and colleagues from Keio University for their generous gift of monoclonal AQP4‐IgG. We thank Zhengqi Lu, Xiaoyan Han, Lisheng Peng, Xiaofen Zhong, and Haixia Wang for their valuable assistance with experimental techniques. This research was supported by grants from the National Natural Science Foundation of China (81771300, 81971140, and 32100787), the National Key R&D Program of China (2022ZD0214300), and the Natural Science Foundation of Guangdong Province (2020A1515010053). Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",
year = "2023",
month = feb,
doi = "10.1002/glia.24271",
language = "English (US)",
volume = "71",
pages = "284--304",
journal = "Glia",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "2",
}