N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination | |
Yu, Xueli1,2,3; Cheng, Gang4; Zhang, Lei1,2,3; Zhang, Yu1,2,3; Wang, Qing1,2,3; Zhao, Mengxue1,2,3; Zeng, Limin1,2,3; 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). |
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