Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination
文献类型：期刊论文
| 作者 | Cui, Xue2; Guo, Yu-e3,4; Fang, Jia-hui2; Shi, Chang-jie2; Suo, Na3,4; Zhang, Ru2; Xie, Xin1,2,4
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2019-11-01 |
| 卷号 | 40期号:11页码:1386-1393 |
| 关键词 | donepezil aricept oligodendrocyte oligodendrocyte progenitor cell differentiation myelin sheaths remyelination CNS demyelinating disorders multiple sclerosis |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-018-0206-4 |
| 通讯作者 | Zhang, Ru(ru.zhang@tongji.edu.cn) ; Xie, Xin(xxie@simm.ac.cn) |
| 英文摘要 | Myelin sheaths play important roles in neuronal functions. In the central nervous system (CNS), the myelin is formed by oligodendrocytes (OLs), which are differentiated from oligodendrocyte precursor cells (OPCs). In CNS demyelinating disorders such as multiple sclerosis (MS), the myelin sheaths are damaged and the remyelination process is hindered. Small molecule drugs that promote OPC to OL differentiation and remyelination may provide a new way to treat these demyelinating diseases. Here we report that donepezil, an acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD), significantly promotes OPC to OL differentiation. Interestingly, other AChEIs, including huperzine A, rivastigmine, and tacrine, have no such effect, indicating that donepezil's effect in promoting OPC differentiation is not dependent on the inhibition of AChE. Donepezil also facilitates the formation of myelin sheaths in OPC-DRG neuron co-culture. More interestingly, donepezil also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone-mediated demyelination animal model. Donepezil is a drug that has been used to treat AD safely for many years; our findings suggest that it might be repurposed to treat CNS demyelinating diseases such as MS by promoting OPC to OL differentiation and remyelination. |
| WOS关键词 | EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS ; NICOTINIC ACETYLCHOLINE-RECEPTORS ; CENTRAL-NERVOUS-SYSTEM ; THYROID-HORMONE ; MYELINATION ; INHIBITORS ; NEUROPROTECTION ; CELL ; ACTIVATION ; GROWTH |
| 资助项目 | Ministry of Science and Technology of China[2015CB964503] ; Ministry of Science and Technology of China[2014CB965002] ; 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[81472862] ; National Natural Science Foundation of China[31501189] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000494974700002 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/281944]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Ru; Xie, Xin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Materia Med, Stake Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Lab Receptor Based Biomed, Shanghai 200092, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Materia Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cui, Xue,Guo, Yu-e,Fang, Jia-hui,et al. Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination[J]. ACTA PHARMACOLOGICA SINICA,2019,40(11):1386-1393. |
| APA | Cui, Xue.,Guo, Yu-e.,Fang, Jia-hui.,Shi, Chang-jie.,Suo, Na.,...&Xie, Xin.(2019).Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination.ACTA PHARMACOLOGICA SINICA,40(11),1386-1393. |
| MLA | Cui, Xue,et al."Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination".ACTA PHARMACOLOGICA SINICA 40.11(2019):1386-1393. |
入库方式： OAI收割
来源：上海药物研究所
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