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学科主题: 基础医学
题名:
Quantitative proteomics reveals that PEA15 regulates astroglial A beta phagocytosis in an Alzheimer′s disease mouse model
作者: Lv, Junniao1; Ma, Shuaipeng1; Zhang, Xuefei1; Zheng, Liangjun1; Ma, Yuanhui1; Zhao, Xuyang2; Lai, Wenjia3; Shen, Hongyan1; Wang, Qingsong1; Ji, Jianguo1
关键词: Quantitative proteomics ; PEA15 ; A beta ; Phagocytosis ; Alzheimer&prime ; s disease ; APP/PS1 mouse
刊名: JOURNAL OF PROTEOMICS
发表日期: 2014-10-14
DOI: 10.1016/j.jprot.2014.07.028
卷: 110, 页:45-58
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemical Research Methods
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: MIGRATION INHIBITORY FACTOR ; AMYLOID-BETA ; GLUTAMINE-SYNTHETASE ; ASTROCYTE MIGRATION ; GLIOMA-CELLS ; IN-VITRO ; PROTEIN ; CLEARANCE ; PEA-15 ; EXPRESSION
英文摘要:

Amyloid-beta (A beta) deposition plays a crucial role in the progression of Alzheimer′s disease (AD). The A beta deposited extracellularly can be phagocytosed and degraded by surrounding activated astrocytes, but the precise mechanisms underlying A beta clearance mediated by astrocytes remain unclear. In this study, we performed tandem mass tag-based quantitative proteomic analysis on the cerebral cortices of 5-month-old APP/PS1 double-transgenic mice. Among the 2668 proteins quantified, 35 proteins were upregulated and 12 were downregulated, with most of these proteins being shown here for the first time to be differently expressed in the APP/PS1 mouse. The altered proteins were involved in molecular transport, lipid metabolism, autophagy, inflammation, and oxidative stress. One specific protein, PEA15 (phosphoprotein enriched in astrocytes 15 kDa) upregulated in APP/PS1 mice, was verified to play a critical role in astrocyte-mediated A beta phagocytosis. Furthermore, PEA15 levels were determined to increase with age in APP/PS1 mice, indicating that A beta stimulated the upregulation of PEA15 in the APP/PS1 mouse. These results highlight the function of PEA15 in astrocyte-mediated A beta phagocytosis, and thus provide novel insight into the molecular mechanism underlying A beta clearance. The protein-expression profile revealed here should offer new clues to understand the pathogenesis of AD and potential therapeutic targets for AD.

Biological significance

Activated astrocytes are known to clear the A beta deposited in the extracellular milieu, which is why they play a key role in regulating the progression of Alzheimer′s disease (AD).However, the molecular mechanism underlying astrocyte-mediated A beta phagocytosis and degradation remains unclear. By performing tandem mass tag-based quantitative proteomic analysis, we identified 47 proteins that were differentially expressed in APP/ PS1 double-transgenic. To our knowledge, this is the first time most of these proteins have been reported to exhibit altered expression in the mouse model of AD. Furthermore, our results indicate that one of the proteins upregulated in the APP/PS1 mouse, PEA15 (phosphoprotein enriched in astrocytes 15 kDa), regulates astroglial phagocytosis of A beta. Our findings provide new insights into the molecular mechanism underlying A beta clearance in AD. The altered profile of protein expression in APP/PS1 mice described here should offer valuable clues to understand the pathogenesis of AD and facilitate the identification of potential targets for the treatment of AD. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 31270872 ; 31470807 ; 31200610 ; 2010CB912203 ; 2011CB915504
项目资助者: National Natural Science Foundation of China ; National Key Basic Research Program of China
WOS记录号: WOS:000345183200005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53703
Appears in Collections:基础医学院_北京大学系统生物医学研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China
2.Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China
3.Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China

Recommended Citation:
Lv, Junniao,Ma, Shuaipeng,Zhang, Xuefei,et al. Quantitative proteomics reveals that PEA15 regulates astroglial A beta phagocytosis in an Alzheimer′s disease mouse model[J]. JOURNAL OF PROTEOMICS,2014,110:45-58.
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