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P2X7 receptor is critical in alpha-synuclein-mediated microglial NADPH oxidase activation
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
2015-07-01
DOI10.1016/j.neurobiolaging.2015.03.015
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
WOS记录号WOS:000355378700009
项目编号2011CB504104 ; 81129018 ; 81430022 ; 81371407 ; 91332107 ; ES016873 ; ES019277
资助机构National Key Basic Research Program of China ; National Natural Science Foundation ; National Institutes of Health
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60867
专题北京大学第三临床医学院
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
推荐引用方式
GB/T 7714
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.
APA Jiang, Tianfang.,Hoekstra, Jake.,Heng, Xin.,Kang, Wenyan.,Ding, Jianqing.,...&Zhang, Jing.(2015).P2X7 receptor is critical in alpha-synuclein-mediated microglial NADPH oxidase activation.NEUROBIOLOGY OF AGING,36(7),2304-2318.
MLA Jiang, Tianfang,et al."P2X7 receptor is critical in alpha-synuclein-mediated microglial NADPH oxidase activation".NEUROBIOLOGY OF AGING 36.7(2015):2304-2318.
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