N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination

doi:10.1038/s41598-018-32326-0

	N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination
	Yu, Xueli 1,2,3; Cheng, Gang 4; Zhang, Lei 1,2,3; Zhang, Yu 1,2,3; Wang, Qing 1,2,3; Zhao, Mengxue 1,2,3; Zeng, Limin 1,2,3; Hu, Youhong4 ; Feng, Linyin1,2,3
刊名	SCIENTIFIC REPORTS
	2018-09-19
卷号	8
ISSN号	2045-2322
DOI	10.1038/s41598-018-32326-0
文献子类	Article
英文摘要	Oligodendrocytes are a type of glial cells that ensheath multiple neuronal axons and form myelin. Under pathological conditions, such as multiple sclerosis (MS), inflammatory damage to myelin and oligodendrocytes leads to demyelination. Although the demyelinated regions can partially resolve functional deficits through remyelination, however, as the disease progresses, remyelination typically becomes incomplete and ultimately fails. One possible explanation for this failure is the activation of the Notch pathway in MS lesions, which impedes oligodendrocyte precursor cells (OPCs) at maturation. This leads to a potential target for remyelination. Here, we have identified a compound Yhhu4952 that promoted the maturation of cultured OPCs in a dose-dependent and time-dependent manner. Neonatal rats showed a significant increase in the expression of myelin basic protein (MBP) and the prevalence of mature oligodendrocytes in the corpus callosum afterYhhu4952 treatment. The compound was also effective in promoting remyelination in cuprizone-induced demyelination model and improving severity scores in experimental autoimmune encephalomyelitis (EAE) model. Mechanism studies revealed that Yhhu4952 promotes OPC differentiation through the inhibition of the Jaggedl-Notchl pathway. These findings suggestYhhu4952 is potentially useful for proceeding oligodendrocyte differentiation and remyelination.
资助项目	Scientific Innovation Project of the Chinese Academy of Sciences[XDA01040304] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA12040304]
WOS关键词	EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS ; CANNABINOID CB2 RECEPTOR ; CENTRAL-NERVOUS-SYSTEM ; MULTIPLE-SCLEROSIS ; DEMYELINATED LESIONS ; ALZHEIMERS-DISEASE ; CNS REMYELINATION ; CYCLING CELLS ; GLIAL-CELLS ; BRAIN
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000445031200023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279577]
专题	药物化学研究室药理学第二研究室
通讯作者	Hu, Youhong; Feng, Linyin
作者单位	1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 2.Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chongzhi Rd, Shanghai 201203, Peoples R China; 3.Shanghai Inst Mat Med, Dept Neuropharmacol, 555 Zu Chongzhi Rd, Shanghai 201203, Peoples R China; 4.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Yu, Xueli,Cheng, Gang,Zhang, Lei,et al. N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination[J]. SCIENTIFIC REPORTS,2018,8.
APA	Yu, Xueli.,Cheng, Gang.,Zhang, Lei.,Zhang, Yu.,Wang, Qing.,...&Feng, Linyin.(2018).N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination.SCIENTIFIC REPORTS,8.
MLA	Yu, Xueli,et al."N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination".SCIENTIFIC REPORTS 8(2018).