LY2940094, an NOPR antagonist, promotes oligodendrocyte generation and myelin recovery in an NOPR independent manner
文献类型：期刊论文
| 作者 | Duan, Yanhui3; Ye, Chenyuan2,3; Liao, Jingyi2,3; Xie, Xin1,2,3
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| 刊名 | NEUROTHERAPEUTICS
 |
| 出版日期 | 2024-09-01 |
| 卷号 | 21期号:5页码:10 |
| 关键词 | LY2940094 Oligodendrocyte Oligodendrocyte progenitor cell Myelin sheath Remyelination Nociceptin/orphanin FQ receptor |
| ISSN号 | 1933-7213 |
| DOI | 10.1016/j.neurot.2024.e00424 |
| 通讯作者 | Xie, Xin(xxie@simm.ac.cn) |
| 英文摘要 | The myelin sheath plays crucial roles in brain development and neuronal functions. In the central nervous system, myelin is generated by oligodendrocytes, that differentiate from oligodendrocyte progenitor cells (OPC). In demyelinating diseases, the differentiation capacity of OPC is impaired and remyelination is dampened. Boosting remyelination by promoting OPC differentiation is a novel strategy for the treatment of demyelinating diseases. The opioid system, which consists of four receptors and their ligands, has been implicated in OPC differentiation and myelin formation. However, the exact roles of each opioid receptor and the relevant pharmacological molecules in OPC differentiation and myelin formation remain elusive. In the present study, specific agonists and antagonists of each opioid receptor were used to explore the function of opioid receptors in OPC differentiation. Nociceptin/orphanin FQ receptor (NOPR) specific antagonist LY2940094 was found to stimulate OPC differentiation and myelination in both in vitro and in vivo models. Unexpectedly, other NOPR ligands did not affect OPC differentiation, and NOPR knockdown did not mimic or impede the effect of LY2940094. LY2940094 was found to modulate the expression of the oligodendrocytes differentiation-associated transcription factors ID4 and Myrf, although the exact mechanism remains unclear. Since LY2940094 has been tested clinically to treat depression and alcohol dependency and has displayed an acceptable safety profile, it may provide an alternative approach to treat demyelinating diseases. |
| WOS关键词 | NOCICEPTIN RECEPTOR ANTAGONIST ; REGULATORY FACTOR ; PROTEIN ; MU ; ADDICTION ; TARGETS ; MEDIATE ; SYSTEM ; KINASE ; CELLS |
| 资助项目 | Ministry of Science and Technology of China[2022ZD0204700] ; Ministry of Science and Technology of China[2022YFA1104700] ; National Natural Science Foundation of China[82121005] |
| WOS研究方向 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001333018100001 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313823]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xie, Xin |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Peoples R China 2.Shanghai Inst Mat Med, Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Duan, Yanhui,Ye, Chenyuan,Liao, Jingyi,et al. LY2940094, an NOPR antagonist, promotes oligodendrocyte generation and myelin recovery in an NOPR independent manner[J]. NEUROTHERAPEUTICS,2024,21(5):10. |
| APA | Duan, Yanhui,Ye, Chenyuan,Liao, Jingyi,&Xie, Xin.(2024).LY2940094, an NOPR antagonist, promotes oligodendrocyte generation and myelin recovery in an NOPR independent manner.NEUROTHERAPEUTICS,21(5),10. |
| MLA | Duan, Yanhui,et al."LY2940094, an NOPR antagonist, promotes oligodendrocyte generation and myelin recovery in an NOPR independent manner".NEUROTHERAPEUTICS 21.5(2024):10. |
入库方式： OAI收割
来源：上海药物研究所
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