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Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases

文献类型：期刊论文

作者Suo, Na2,4; Guo, Yu-e2,4; He, Bingqing2,3,4; Gu, Haifeng4; Xie, Xin1,3,4
刊名GLIA
出版日期2019-07-01
卷号67期号:7页码:1320-1332
ISSN号0894-1491
关键词differentiation ERK MAPK MEK inhibitor myelin oligodendrocyte oligodendrocyte progenitor cell remyelination
DOI10.1002/glia.23606
通讯作者Xie, Xin(xxie@simm.ac.cn)
英文摘要Oligodendrocytes (OLs) are the myelinating glia of the central nervous system. Injury to OLs causes myelin loss. In demyelinating diseases, such as multiple sclerosis, the remyelination is hindered principally due to a failure of the oligodendrocyte precursor cells (OPCs) to differentiate into mature OLs. To identify inducers of OPC to OL differentiation, a high-throughput screening based on myelin basic protein expression using neural progenitor cells-derived OPCs has been performed and, PD0325901-an MEK (MAPK kinase) inhibitor-is found to significantly enhance OPC to OL differentiation in a dose- and time-dependent manner. Other MEK inhibitors also display similar effect, indicating blockade of MAPK-ERK signaling is sufficient to induce OPC differentiation into OLs. PD0325901 facilitates the formation of myelin sheaths in OPC-neuron co-culture in vitro. And in experimental autoimmune encephalomyelitis model and cuprizone-induced demyelination model, PD0325901 displays significant therapeutic effect by promoting myelin regeneration. Our results suggest that targeting the MAPK-ERK pathway might be an intriguing way to develop new therapies for demyelinating diseases.
WOS关键词SIGNAL-REGULATED KINASE ; KAPPA-OPIOID RECEPTOR ; MATURE OLIGODENDROCYTES ; LINEAGE PROGRESSION ; PROGENITOR CELLS ; MYELIN THICKNESS ; ERK1/2 MAPK ; DIFFERENTIATION ; REMYELINATION ; CNS
资助项目Ministry of Science and Technology of China[2015CB964503] ; Ministry of Science and Technology of China[2017YFA0104002] ; Chinese Academy of Sciences[XDA16010202] ; National Natural Science Foundation of China[81425024] ; National Natural Science Foundation of China[81730099] ; National Natural Science Foundation of China[81472862]
WOS研究方向Neurosciences & Neurology
语种英语
出版者WILEY
WOS记录号WOS:000467979400007
源URL[http://119.78.100.183/handle/2S10ELR8/289788]  
专题新药研究国家重点实验室
通讯作者Xie, Xin
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Stake Key Lab Drug Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Suo, Na,Guo, Yu-e,He, Bingqing,et al. Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases[J]. GLIA,2019,67(7):1320-1332.
APA Suo, Na,Guo, Yu-e,He, Bingqing,Gu, Haifeng,&Xie, Xin.(2019).Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases.GLIA,67(7),1320-1332.
MLA Suo, Na,et al."Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases".GLIA 67.7(2019):1320-1332.

入库方式： OAI收割

来源：上海药物研究所

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