Huperzine A Alleviates Synaptic Deficits and Modulates Amyloidogenic and Nonamyloidogenic Pathways in APPswe/PS1dE9 Transgenic Mice
文献类型：期刊论文
| 作者 | Wang, Ying; Tang, Xi Can; Zhang, Hai Yan |
| 刊名 | JOURNAL OF NEUROSCIENCE RESEARCH
 |
| 出版日期 | 2012-02 |
| 卷号 | 90期号:2页码:508-517 |
| 关键词 | Alzheimer's disease huperzine A beta-amyloid ADAM10 BACE1 |
| ISSN号 | 0360-4012 |
| DOI | 10.1002/jnr.22775 |
| 文献子类 | Article |
| 英文摘要 | Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) used in the treatment of Alzheimer's disease (AD). Recently, HupA was shown to be active in modulating the nonamyloidogenic metabolism of beta-amyloid precursor protein (APP) in APP-transfected human embryonic kidney cell line (HEK293swe). However, in vivo research concerning the mechanism of HupA in APP transgenic mice has not yet been fully elucidated. The present study indicates that the loss of dendritic spine density and synaptotagmin levels in the brain of APPswe/presenilin-1 (PS1) transgenic mice was significantly ameliorated by chronic HupA treatment and provides evidence that this neuroprotection was associated with reduced amyloid plaque burden and oligomeric beta-amyloid (Ab) levels in the cortex and hippocampus of APPswe/PS1dE9 transgenic mice. Our findings further demonstrate that the amelioration effect of HupA on Ab deposits may be mediated, at least in part, by regulation of the compromised expression of a disintegrin and metalloprotease 10 (ADAM10) and excessive membrane trafficking of beta-site APP cleavage enzyme 1 (BACE1) in these transgenic mice. In addition, extracellular signal-regulated kinases 1/2 (Erk1/2) phosphorylation may also be partially involved in the effect of HupA on APP processing. In conclusion, our work for the first time demonstrates the neuroprotective effect of HupA on synaptic deficits in APPswe/PS1dE9 transgenic mice and further clarifies the potential pharmacological targets for this protective effect, in which modulation of nonamyloidogenic and amyloidogenic APP processing pathways may be both involved. These findings may provide adequate evidence for the clinical and experimental benefits gained from HupA treatment. (C) 2011 Wiley Periodicals, Inc. |
| WOS关键词 | ACTIVATED-PROTEIN-KINASE ; MUSCARINIC ACETYLCHOLINE-RECEPTORS ; DENDRITIC SPINE LOSS ; PRECURSOR-PROTEIN ; ALZHEIMERS-DISEASE ; MOUSE MODEL ; ALPHA-SECRETASE ; BETA-PEPTIDE ; TG2576 MICE ; C-ALPHA |
| 资助项目 | National Natural Science Foundation of China[30801402] ; National Natural Science Foundation of China[81072646] ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry[00000000] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2009ZX09301-001] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2009ZX09301-063] ; Shanghai Science and Technology Development Funds[10QA1408100] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000299072300017 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278209]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Zhang, Hai Yan |
| 作者单位 | Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Ying,Tang, Xi Can,Zhang, Hai Yan. Huperzine A Alleviates Synaptic Deficits and Modulates Amyloidogenic and Nonamyloidogenic Pathways in APPswe/PS1dE9 Transgenic Mice[J]. JOURNAL OF NEUROSCIENCE RESEARCH,2012,90(2):508-517. |
| APA | Wang, Ying,Tang, Xi Can,&Zhang, Hai Yan.(2012).Huperzine A Alleviates Synaptic Deficits and Modulates Amyloidogenic and Nonamyloidogenic Pathways in APPswe/PS1dE9 Transgenic Mice.JOURNAL OF NEUROSCIENCE RESEARCH,90(2),508-517. |
| MLA | Wang, Ying,et al."Huperzine A Alleviates Synaptic Deficits and Modulates Amyloidogenic and Nonamyloidogenic Pathways in APPswe/PS1dE9 Transgenic Mice".JOURNAL OF NEUROSCIENCE RESEARCH 90.2(2012):508-517. |
入库方式： OAI收割
来源：上海药物研究所
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