2,2',4'-Trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice
文献类型：期刊论文
| 作者 | Zhu, Zhiyuan; Li, Chenjing; Wang, Xu; Yang, Zhengyi; Chen, Jing ; Hu, Lihong; Jiang, Hualiang; Shen, Xu
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| 刊名 | JOURNAL OF NEUROCHEMISTRY
 |
| 出版日期 | 2010-07 |
| 卷号 | 114期号:2页码:374-385 |
| 关键词 | Alzheimer's disease amyloid-beta inhibitor transgenic mice trihydroxychalcone beta-site amyloid precursor protein-cleaving enzyme 1 (beta-secretase) |
| ISSN号 | 0022-3042 |
| DOI | 10.1111/j.1471-4159.2010.06751.x |
| 文献子类 | Article |
| 英文摘要 | P>Alzheimer's disease (AD) characterizes a progressive neurodegenerative disorder of the brain, while AD patients are afflicted with irreversible loss of neurons and further the intellectual abilities including memory and reasoning. One of the typical hallmarks of AD is the deposition of senile plaque that is contributed mainly by amyloid-beta (A beta), whose production is initiated by beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1). Inhibition of BACE1 is thereby regarded as an attractive strategy for anti-AD drug discovery. Here, we reported that the natural product 2,2',4'-trihydroxychalcone (TDC) from Glycyrrhiza glabra functioned as a specific non-competitive inhibitor against BACE1 enzyme, and potently repressed beta-cleavage of APP and production of A beta in human embryo kidney cells-APPswe cells. Moreover, the amelioration ability of this compound against the in vivo memory impairment was further evaluated by APP-PS1 double transgenic mice model. It is discovered that treatment of 9 mg/kg/day of TDC could obviously decrease A beta production and A beta plaque formation, while efficiently improve the memory impairment based on Morris water maze test. Our findings thus demonstrated that the natural product TDC as a new BACE1 inhibitor could ameliorate memory impairment in mice, and is expected to be potentially used as a lead compound for further anti-AD reagent development. |
| WOS关键词 | AMYLOID PRECURSOR PROTEIN ; HUMAN BETA-SECRETASE ; X-RAY-STRUCTURE ; ALZHEIMERS-DISEASE ; IN-VIVO ; TRANSGENIC MICE ; PEPTIDOMIMETIC INHIBITORS ; MOUSE MODEL ; DESIGN ; POTENT |
| 资助项目 | State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2007AA02Z147] ; National Natural Science Foundation of China[30925040] ; National Natural Science Foundation of China[30890044] ; National Natural Science Foundation of China[20721003] ; Key New Drug Creation and Manufacturing Program[2009ZX09301-001] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000279077900004 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278860]  |
| 专题 | 上海中药现代化研究中心 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 药理学第三研究室 |
| 通讯作者 | Hu, Lihong |
| 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 | Zhu, Zhiyuan,Li, Chenjing,Wang, Xu,et al. 2,2',4'-Trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice[J]. JOURNAL OF NEUROCHEMISTRY,2010,114(2):374-385. |
| APA | Zhu, Zhiyuan.,Li, Chenjing.,Wang, Xu.,Yang, Zhengyi.,Chen, Jing.,...&Shen, Xu.(2010).2,2',4'-Trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice.JOURNAL OF NEUROCHEMISTRY,114(2),374-385. |
| MLA | Zhu, Zhiyuan,et al."2,2',4'-Trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice".JOURNAL OF NEUROCHEMISTRY 114.2(2010):374-385. |
入库方式： OAI收割
来源：上海药物研究所
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