Calpain Activation Promotes BACE1 Expression, Amyloid Precursor Protein Processing, and Amyloid Plaque Formation in a Transgenic Mouse Model of Alzheimer Disease
文献类型：期刊论文
| 作者 | Luo, Zhen-Ge
|
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2010 |
| 卷号 | 285期号:36页码:27737-27744 |
| 关键词 | BETA-SECRETASE ACTIVITY IN-VIVO BRAIN-INJURY WATER-MAZE MICE PRESENILIN-1 NEURODEGENERATION DEPOSITION CALCIUM P25 |
| ISSN号 | 0021-9258 |
| 通讯作者 | Luo, ZG (reprint author), Chinese Acad Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,zgluo@ion.ac.cn |
| 英文摘要 | Abnormal activation of calpain is implicated in synaptic dysfunction and participates in neuronal death in Alzheimer disease (AD) and other neurological disorders. Pharmacological inhibition of calpain has been shown to improve memory and synaptic transmission in the mouse model of AD. However, the role and mechanism of calpain in AD progression remain elusive. Here we demonstrate a role of calpain in the neuropathology in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice, an established mouse model of AD. We found that overexpression of endogenous calpain inhibitor calpastatin (CAST) under the control of the calcium/calmodulindependent protein kinase II promoter in APP/PS1 mice caused a remarkable decrease of amyloid plaque burdens and prevented Tau phosphorylation and the loss of synapses. Furthermore, CAST overexpression prevented the decrease in the phosphorylation of the memory-related molecules CREB and ERK in the brain of APP/PS1 mice and improved spatial learning and memory. Interestingly, treatment of cultured primary neurons with amyloid-beta (A beta) peptides caused an increase in the level of beta-site APP-cleaving enzyme 1 (BACE1), the key enzyme responsible for APP processing and A beta production. This effect was inhibited by CAST overexpression. Consistently, overexpression of calpain in heterologous APP expressing cells up-regulated the level of BACE1 and increased A beta production. Finally, CAST transgene prevented the increase of BACE1 in APP/PS1 mice. Thus, calpain activation plays an important role in APP processing and plaque formation, probably by regulating the expression of BACE1. |
| 学科主题 | Biochemistry & Molecular Biology |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China[30721004, 30825013]; National Basic Research Program[2006CB806600, 2011CB809002]; Key State Research Program of China[2006CB943900]; Chinese Academy of Sciences[KSCX2-YW-R-102]; Program of Shanghai Subject Chief Scientist[08XD14050] |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1575]  |
| 专题 | 上海神经科学研究所_神经所(总) 上海神经科学研究所_突触信号研究组 |
| 推荐引用方式 GB/T 7714 | Luo, Zhen-Ge. Calpain Activation Promotes BACE1 Expression, Amyloid Precursor Protein Processing, and Amyloid Plaque Formation in a Transgenic Mouse Model of Alzheimer Disease[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(36):27737-27744. |
| APA | Luo, Zhen-Ge.(2010).Calpain Activation Promotes BACE1 Expression, Amyloid Precursor Protein Processing, and Amyloid Plaque Formation in a Transgenic Mouse Model of Alzheimer Disease.JOURNAL OF BIOLOGICAL CHEMISTRY,285(36),27737-27744. |
| MLA | Luo, Zhen-Ge."Calpain Activation Promotes BACE1 Expression, Amyloid Precursor Protein Processing, and Amyloid Plaque Formation in a Transgenic Mouse Model of Alzheimer Disease".JOURNAL OF BIOLOGICAL CHEMISTRY 285.36(2010):27737-27744. |
入库方式： OAI收割
来源：上海神经科学研究所
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