A Peptide Binding to the beta-Site of APP Improves Spatial Memory and Attenuates A beta Burden in Alzheimer's Disease Transgenic Mice
文献类型:期刊论文
作者 | Yang, Shi-gao2; Wang, Shao-wei1,2; Zhao, Min2; Zhang, Ran2; Zhou, Wei-wei2; Li, Ya-nan2,3; Su, Ya-jing2,3; Zhang, He2; Yu, Xiao-lin1; Liu, Rui-tian1,2 |
刊名 | PLOS ONE
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出版日期 | 2012-11-01 |
卷号 | 7期号:11页码:文献号: e48540 |
关键词 | AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME-1 BACE1 LONG-TERM POTENTIATION SINGLE-CHAIN ANTIBODY GAMMA-SECRETASE MOUSE MODEL THERAPEUTIC TARGET ALPHA-SECRETASE CELL BIOLOGY IN-VITRO |
ISSN号 | 1932-6203 |
通讯作者 | Yu, XL |
英文摘要 | Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into beta-amyloid (A beta); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the beta-proteolytic site on APP and Ab N-terminal. The S1 peptide significantly reduced A beta levels in vitro and in vivo and inhibited A beta cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Ab burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Ab generation and inhibiting Ab cytotoxicity. |
WOS标题词 | Science & Technology |
类目[WOS] | Multidisciplinary Sciences |
研究领域[WOS] | Science & Technology - Other Topics |
关键词[WOS] | AMYLOID PRECURSOR PROTEIN ; CLEAVING ENZYME-1 BACE1 ; LONG-TERM POTENTIATION ; SINGLE-CHAIN ANTIBODY ; GAMMA-SECRETASE ; MOUSE MODEL ; THERAPEUTIC TARGET ; ALPHA-SECRETASE ; CELL BIOLOGY ; IN-VITRO |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000310601300018 |
公开日期 | 2013-10-11 |
版本 | 出版稿 |
源URL | [http://ir.ipe.ac.cn/handle/122111/3153] ![]() |
专题 | 过程工程研究所_生化工程国家重点实验室 |
作者单位 | 1.Chinese Acad Sci, Natl Key Lab Biochem Engn, Inst Proc Engn, Beijing, Peoples R China 2.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China 3.Ningxia Univ, Sch Life Sci, Yinchuan, Peoples R China |
推荐引用方式 GB/T 7714 | Yang, Shi-gao,Wang, Shao-wei,Zhao, Min,et al. A Peptide Binding to the beta-Site of APP Improves Spatial Memory and Attenuates A beta Burden in Alzheimer's Disease Transgenic Mice[J]. PLOS ONE,2012,7(11):文献号: e48540. |
APA | Yang, Shi-gao.,Wang, Shao-wei.,Zhao, Min.,Zhang, Ran.,Zhou, Wei-wei.,...&Liu, Rui-tian.(2012).A Peptide Binding to the beta-Site of APP Improves Spatial Memory and Attenuates A beta Burden in Alzheimer's Disease Transgenic Mice.PLOS ONE,7(11),文献号: e48540. |
MLA | Yang, Shi-gao,et al."A Peptide Binding to the beta-Site of APP Improves Spatial Memory and Attenuates A beta Burden in Alzheimer's Disease Transgenic Mice".PLOS ONE 7.11(2012):文献号: e48540. |
入库方式: OAI收割
来源:过程工程研究所
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