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

doi:10.1002/glia.23606

	Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases
	Suo, Na 1,2; Guo, Yu-e 1,2; He, Bingqing1,2,3 ; Gu, Haifeng 1; Xie, Xin1,3,4
	2019-07
发表期刊	GLIA
ISSN	0894-1491
卷号	67 期号:7 页码:1320-1332
发表状态	已发表
DOI	10.1002/glia.23606
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.
关键词	differentiation ERK MAPK MEK inhibitor myelin oligodendrocyte oligodendrocyte progenitor cell remyelination
收录类别	SCI ; SCIE
语种	英语
资助项目	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
WOS类目	Neurosciences
WOS记录号	WOS:000467979400007
出版者	WILEY
WOS关键词	SIGNAL-REGULATED KINASE ; KAPPA-OPIOID RECEPTOR ; MATURE OLIGODENDROCYTES ; LINEAGE PROGRESSION ; PROGENITOR CELLS ; MYELIN THICKNESS ; ERK1/2 MAPK ; DIFFERENTIATION ; REMYELINATION ; CNS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/40899
专题	生命科学与技术学院_特聘教授组_谢欣组生命科学与技术学院_博士生
通讯作者	Xie, Xin
作者单位	1.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 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, Stake Key Lab Drug Res, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
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.