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学科主题: 临床医学
题名:
alpha-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation
作者: Wang, Shijun1,2; Chu, Chun-Hsien2; Stewart, Tessandra1; Ginghina, Carmen1; Wang, Yifei3,4; Nie, Hui2; Guo, Mingri2; Wilson, Belinda2; Hong, Jau-Shyong2; Zhang, Jing1,5,6
关键词: alpha-Synuclein ; microglial chemotaxis ; neuroinflammation ; Lyn ; hydrogen peroxide
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2015-04-14
DOI: 10.1073/pnas.1417883112
卷: 112, 期:15, 页:E1926-E1935
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: PARKINSONS-DISEASE ; IN-VITRO ; INDUCED ACTIVATION ; REDOX SENSOR ; INFLAMMATION ; NEUTROPHILS ; INHIBITION ; NEURONS ; NEURODEGENERATION ; REGENERATION
英文摘要:

Malformed alpha-Synuclein (alpha-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in alpha-synucleinopathies, such as Parkinson′s disease. The mechanisms by which alpha-syn aggregates activate and recruit microglia remain unclear, however. Here we show that alpha-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when alpha-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin-associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that alpha-syn-mediated microglial migration reaches beyond Parkinson′s disease.

语种: 英语
所属项目编号: R01 ES019277 ; R01 ES016873 ; 81129018
项目资助者: NIEHS ; National Institutes of Health ; National Natural Science Foundation of China
WOS记录号: WOS:000352856800017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57976
Appears in Collections:北京大学第三临床医学院_病理科_期刊论文

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作者单位: 1.Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA
2.East Chapel Hill High Sch, Chapel Hill, NC 27514 USA
3.NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA
4.Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA
5.Peking Univ, Hosp 3, Dept Pathol, Beijing 100191, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Shijun,Chu, Chun-Hsien,Stewart, Tessandra,et al. alpha-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(15):E1926-E1935.
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