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Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway

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Abstract

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31771129).

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Author notes

  1. Qi Shao, Ming Zhao, and Wenwen Pei contributed equally to this work.

Authors and Affiliations

  1. Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Naval Medical University, Shanghai, 200433, China

    Qi Shao, Ming Zhao, Wenwen Pei, Yingyan Pu, Mingdong Liu, Weili Liu, Zhongwang Yu, Kefu Chen, Hong Liu & Li Cao

  2. Changhai Stroke Center, Changhai Hospital, Naval Medical University, Shanghai, 200433, China

    Ming Zhao & Benqiang Deng

  3. The 983rd Hospital of Joint Logistics Support Forces of the PLA, Tianjin, 300142, China

    Ming Zhao

  4. The 988th Hospital of Joint Logistics Support Forces of the PLA, Zhengzhou, 450000, China

    Kefu Chen

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  1. Qi Shao
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Shao, Q., Zhao, M., Pei, W. et al. Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway. Neurosci. Bull. 37, 1314–1324 (2021). https://doi.org/10.1007/s12264-021-00696-7

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