donepeziladrugforalzheimersdiseasepromotesoligodendrocytegenerationandremyelination

doi:10.1038/s41401-018-0206-4

	donepeziladrugforalzheimersdiseasepromotesoligodendrocytegenerationandremyelination
	Cui Xue 1; Guo Yue 2; Fang Jiahui 1; Shi Changjie 1; Suo Na 2; Zhang Ru 1; Xie Xin 1
刊名	actapharmacologicasinica
	2019
卷号	40 期号:11 页码:1386
关键词	EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS NICOTINIC ACETYLCHOLINE-RECEPTORS CENTRAL-NERVOUS-SYSTEM THYROID-HORMONE MYELINATION INHIBITORS NEUROPROTECTION CELL ACTIVATION GROWTH 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
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.
资助项目	[Ministry of Science and Technology of China] ; [Chinese Academy of Sciences] ; [National Natural Science Foundation of China]
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280680]
专题	中国科学院上海药物研究所
作者单位	1.同济大学 2.中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Cui Xue,Guo Yue,Fang Jiahui,et al. donepeziladrugforalzheimersdiseasepromotesoligodendrocytegenerationandremyelination[J]. actapharmacologicasinica,2019,40(11):1386.
APA	Cui Xue.,Guo Yue.,Fang Jiahui.,Shi Changjie.,Suo Na.,...&Xie Xin.(2019).donepeziladrugforalzheimersdiseasepromotesoligodendrocytegenerationandremyelination.actapharmacologicasinica,40(11),1386.
MLA	Cui Xue,et al."donepeziladrugforalzheimersdiseasepromotesoligodendrocytegenerationandremyelination".actapharmacologicasinica 40.11(2019):1386.