Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway
作者机构：Institute of NeuroscienceKey Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain ScienceNaval Medical UniversityShanghai 200433China Changhai Stroke CenterChanghai HospitalNaval Medical UniversityShanghai 200433China The 983rd Hospital of Joint Logistics Support Forces of the PLATianjin 300142China The 988th Hospital of Joint Logistics Support Forces of the PLAZhengzhou 450000China
出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)
年 卷 期：2021年第37卷第9期
页 面：1314-1324页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学]
基 金：This work was supported by the National Natural Science Foundation of China(31771129).
主 题：Pinocembrin Oligodendrocytes Differentiation Remyelination MTOR
摘 要：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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