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学科主题: 临床医学
题名:
P2X7 receptor is critical in alpha-synuclein-mediated microglial NADPH oxidase activation
作者: Jiang, Tianfang1,2; Hoekstra, Jake3; Heng, Xin1,2; Kang, Wenyan1,2; Ding, Jianqing1,2; Liu, Jun1,2; Chen, Shengdi1,2,4,5; Zhang, Jing3,6
关键词: Parkinson&prime ; s disease ; Microglia ; alpha-Synuclein ; P2X7 receptor ; PI3K/AKT signaling
刊名: NEUROBIOLOGY OF AGING
发表日期: 2015-07-01
DOI: 10.1016/j.neurobiolaging.2015.03.015
卷: 36, 期:7, 页:2304-2318
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Geriatrics & Gerontology ; Neurosciences
研究领域[WOS]: Geriatrics & Gerontology ; Neurosciences & Neurology
关键词[WOS]: PARKINSONS-DISEASE ; OXIDATIVE STRESS ; DOPAMINERGIC NEURODEGENERATION ; INDUCED APOPTOSIS ; P2X(7) RECEPTORS ; INDUCE APOPTOSIS ; NEURONAL DEATH ; EXPRESSION ; CELLS ; MODEL
英文摘要:

Activated microglia are commonly observed in individuals with neurodegenerative disorders, including Parkinson′s disease (PD) and are believed to contribute to neuronal death. This process occurs at least due partially to nicotinamide adenine dinucleotide phosphate oxidase (PHOX) activation, which leads to the production of superoxide and oxidative stress. alpha-Synuclein (alpha-Syn), a key protein implicated in PD pathogenesis, can activate microglia, contributing to death of dopaminergic neurons. Here, microglial cells (BV2) and primary cultured microglia were used to study the role that the purinergic receptor P2X7 plays in recognizing alpha-Syn and promoting PHOX activation. We demonstrate that both wild type and A53T mutant alpha-Syn readily activate PHOX, with the A53T form producing more rapid and sustained effects, that is, oxidative stress and cellular injuries. Furthermore, this process involves the activation of phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) pathway. Thus, it is concluded that stimulation of the microglial P2X7 receptor by extracellular a-Syn, with PI3K/AKT activation and increased oxidative stress, could be an important mechanism and a potential therapeutic target for PD. (C) 2015 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 2011CB504104 ; 81129018 ; 81430022 ; 81371407 ; 91332107 ; ES016873 ; ES019277
项目资助者: National Key Basic Research Program of China ; National Natural Science Foundation ; National Institutes of Health
WOS记录号: WOS:000355378700009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60867
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Dept Neurol, Shanghai 200025, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Inst Neurol, Shanghai 200025, Peoples R China
3.Univ Washington, Dept Pathol, Seattle, WA 98195 USA
4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Dept Neurol,Lab Neurodegenerat Dis, Shanghai, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Hosp 3, Dept Pathol,Inst Basic Sci, Beijing 100871, Peoples R China

Recommended Citation:
Jiang, Tianfang,Hoekstra, Jake,Heng, Xin,et al. P2X7 receptor is critical in alpha-synuclein-mediated microglial NADPH oxidase activation[J]. NEUROBIOLOGY OF AGING,2015,36(7):2304-2318.
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