Decreased Accumulation of Subcellular Amyloid-beta with Improved Mitochondrial Function Mediates the Neuroprotective Effect of Huperzine A
文献类型：期刊论文
| 作者 | Yang, Ling; Ye, Chun-yan; Huang, Xiao-tian; Tang, Xi-can ; Zhang, Hai-yan
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| 刊名 | JOURNAL OF ALZHEIMERS DISEASE
 |
| 出版日期 | 2012 |
| 卷号 | 31期号:1页码:131-142 |
| 关键词 | Alzheimer's disease amyloid-beta peptide huperzine A mitochondrial dysfunction oligomer |
| ISSN号 | 1387-2877 |
| DOI | 10.3233/JAD-2012-120274 |
| 文献子类 | Article |
| 英文摘要 | A number of recent discoveries indicate that huperzine A, an active herbal medicine employed for the treatment of Alzheimer's disease (AD) in China, can afford neuroprotection on in vitro and in vivo models related to mitochondrial dysfunction. However, it is an intricate and highly debated research topic about whether another pharmacological mechanism is involved in the beneficial profiles of huperzine A, independent of its well-recognized potent acetycholinesterase (AChE) inhibitory effect. As an extension, this study for the first time verified the co-occurrence of the beneficial effects of huperzine A on mitochondrial dysfunction and memory deficits in A beta PP/PS1 double transgenic mice, at a time point that AChE was not inhibited. Moreover, using isolated brain cortical mitochondria, we confirmed the ameliorating effect of huperzine A on oligomeric A beta(1-42)-induced ATP reduction and mitochondrial swelling, as well as a decrease in the enzymatic activities of respiratory chain complexes, especially complex II-III and complex IV, which may be attributed to the blockage of oligomeric A beta(1-42) from penetrating into mitochondria. These results shed more light on a potential direct target of huperzine A on isolated mitochondria, which may be largely different from its specific inhibition on AChE. This work describes a novel mechanism of neuroprotection by huperzine A and provides important clues for discovering novel therapeutic strategy for AD. |
| WOS关键词 | TRANSGENIC MOUSE MODEL ; ALZHEIMERS-DISEASE ; A-BETA ; ATTENUATES MITOCHONDRIAL ; PERMEABILITY TRANSITION ; COGNITIVE IMPAIRMENT ; NEURONAL APOPTOSIS ; BRAIN MITOCHONDRIA ; PRECURSOR PROTEIN ; MICE |
| 资助项目 | Ministry of Science and Technology of China[2011CB510004] ; 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[2012ZX09301001-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2012ZX09301001-004] ; SKLDR/SIMM Projects[SIMM1105KF-04] ; Shanghai Science and Technology Development Funds[10QA1408100] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000306122900013 |
| 出版者 | IOS PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278251]  |
| 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 |
| 通讯作者 | Zhang, Hai-yan |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Ling,Ye, Chun-yan,Huang, Xiao-tian,et al. Decreased Accumulation of Subcellular Amyloid-beta with Improved Mitochondrial Function Mediates the Neuroprotective Effect of Huperzine A[J]. JOURNAL OF ALZHEIMERS DISEASE,2012,31(1):131-142. |
| APA | Yang, Ling,Ye, Chun-yan,Huang, Xiao-tian,Tang, Xi-can,&Zhang, Hai-yan.(2012).Decreased Accumulation of Subcellular Amyloid-beta with Improved Mitochondrial Function Mediates the Neuroprotective Effect of Huperzine A.JOURNAL OF ALZHEIMERS DISEASE,31(1),131-142. |
| MLA | Yang, Ling,et al."Decreased Accumulation of Subcellular Amyloid-beta with Improved Mitochondrial Function Mediates the Neuroprotective Effect of Huperzine A".JOURNAL OF ALZHEIMERS DISEASE 31.1(2012):131-142. |
入库方式： OAI收割
来源：上海药物研究所
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