Donepezil,a drug for Alzheimer’s disease,promotes oligodendrocyte generation and remyelination  

作　　者：Xue Cui Yu-e Guo Jia-hui Fang Chang-jie Shi Na Suo Ru Zhang Xin Xie 

机构地区：[1]Shanghai Key Laboratory of Signaling and Disease Research,Laboratory of Receptor-based Bio-medicine,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China [2]CAS Key Laboratory of Receptor Research,the National Center for Drug Screening,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]University of Chinese Academy of Sciences,No.19A Yuquan Road,Beijing 100049,China [4]Stake Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Acta Pharmacologica Sinica》2019年第11期1386-1393,共8页中国药理学报（英文版）

基　　金：grants from the Ministry of Science and Technology of China(No.2015CB964503,2014CB965002,and 2017YFA0104002);the Chinese Academy of Sciences(No.XDA16010202);the National Natural Science Foundation of China(Nos.81425024,81472862,and 31501189).

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 AChEls,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.

关 键 词：DONEPEZIL ARICEPT OLIGODENDROCYTE OLIGODENDROCYTE progenitor cell differentiation MYELIN sheaths REMYELINATION CNS DEMYELINATING disorders multiple sclerosis 

分 类 号：R74[医药卫生—神经病学与精神病学]