Donepezil attenuates A beta-associated mitochondrial dysfunction and reduces mitochondrial A beta accumulation in vivo and in vitro
文献类型：期刊论文
| 作者 | Ye, Chun Yan; Lei, Yun; Tang, Xi Can; Zhang, Hai Yan |
| 刊名 | NEUROPHARMACOLOGY
 |
| 出版日期 | 2015-08 |
| 卷号 | 95页码:29-36 |
| 关键词 | Alzheimer's disease Donepezil Amyloid-beta Oligomer Mitochondrial dysfunction |
| ISSN号 | 0028-3908 |
| DOI | 10.1016/j.neuropharm.2015.02.020 |
| 文献子类 | Article |
| 英文摘要 | The main purpose of the present study is to investigate the influence of donepezil, a well-known acetylcholinesterase (AChE) inhibitor, on amyloid-beta (A beta)-associated mitochondrial dysfunction, in order to gain a better understanding of the neuroprotective effects of this clinically used anti-Alzheimer's disease (AD) drug. First, our study verifies the ameliorative effects of donepezil on behavioral deficits in both working memory and anxiety in APP/PS1 double transgenic mice, at a time point that AChE is not inhibited. Meanwhile, we demonstrate that donepezil enhances the resistance of brain mitochondria of APP/PS1 mice to the induction of rnitochondrial permeability transition (MPT) by calcium ions. Moreover, the level of mitochondrial A beta in the brain of donepezil-treated APP/PS1 transgenic mice is significantly lower than that of vehicle-treated APP/PS1 mice. Our in vitro study using isolated mitochondria from rat brains, which is expected as an AChE-free subcellular system, further confirms the ameliorative effects of donepezil on oligomeric AP(1-42) induced mitochondrial swelling and ATP reduction. In addition, donepezil treatment also significantly blocks the A beta accumulation in the isolated mitochondria. Our study reported for the first time that the protective effects of donepezil against A beta-associated mitochondrial dysfunction are closely associated with the reduction of A beta accumulation in the mitochondria. Above observation led us to assume that, besides potent AChE inhibitory effect, other non-cholinergic mechanisms may be involved in the neuroprotective profiles of donepezil. (C) 2015 Elsevier Ltd. All rights reserved. |
| WOS关键词 | CYTOCHROME-C RELEASE ; ALZHEIMERS-DISEASE ; AMYLOID-BETA ; MOUSE MODEL ; COGNITIVE IMPAIRMENT ; TRANSGENIC MICE ; T-MAZE ; MEMORY ; PEPTIDE ; HUPERZINE |
| 资助项目 | National Natural Science Foundation of China[81173034] ; National Natural Science Foundation of China[81072646] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2012ZX09301001-004] ; Ministry of Science and Technology of China[2011CB510004] |
| WOS研究方向 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000357349100004 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276459]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Zhang, Hai Yan |
| 作者单位 | Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Chun Yan,Lei, Yun,Tang, Xi Can,et al. Donepezil attenuates A beta-associated mitochondrial dysfunction and reduces mitochondrial A beta accumulation in vivo and in vitro[J]. NEUROPHARMACOLOGY,2015,95:29-36. |
| APA | Ye, Chun Yan,Lei, Yun,Tang, Xi Can,&Zhang, Hai Yan.(2015).Donepezil attenuates A beta-associated mitochondrial dysfunction and reduces mitochondrial A beta accumulation in vivo and in vitro.NEUROPHARMACOLOGY,95,29-36. |
| MLA | Ye, Chun Yan,et al."Donepezil attenuates A beta-associated mitochondrial dysfunction and reduces mitochondrial A beta accumulation in vivo and in vitro".NEUROPHARMACOLOGY 95(2015):29-36. |
入库方式： OAI收割
来源：上海药物研究所
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