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学科主题临床医学
alpha-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation
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
2015-04-14
DOI10.1073/pnas.1417883112
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
WOS记录号WOS:000352856800017
项目编号R01 ES019277 ; R01 ES016873 ; 81129018
资助机构NIEHS ; National Institutes of Health ; National Natural Science Foundation of China
引用统计
被引频次:33[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/400002259/57976
专题北京大学第三临床医学院_病理科
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
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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.
APA Wang, Shijun.,Chu, Chun-Hsien.,Stewart, Tessandra.,Ginghina, Carmen.,Wang, Yifei.,...&Zhang, Jing.(2015).alpha-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(15),E1926-E1935.
MLA Wang, Shijun,et al."alpha-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.15(2015):E1926-E1935.
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