The Experts below are selected from a list of 2247 Experts worldwide ranked by ideXlab platform
Jing Zhang - One of the best experts on this subject based on the ideXlab platform.
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α synuclein a chemoattractant directs microglial migration via h2o2 dependent Lyn phosphorylation
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Shijun Wang, Chun Hsien Chu, Tessandra Stewart, Carmen Ginghina, Yifei Wang, Hui Nie, Mingri Guo, Belinda Wilson, Jaushyong Hong, Jing ZhangAbstract:Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-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 α-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 α-syn–mediated microglial migration reaches beyond Parkinson’s disease.
Shijun Wang - One of the best experts on this subject based on the ideXlab platform.
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α synuclein a chemoattractant directs microglial migration via h2o2 dependent Lyn phosphorylation
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Shijun Wang, Chun Hsien Chu, Tessandra Stewart, Carmen Ginghina, Yifei Wang, Hui Nie, Mingri Guo, Belinda Wilson, Jaushyong Hong, Jing ZhangAbstract:Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-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 α-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 α-syn–mediated microglial migration reaches beyond Parkinson’s disease.
Shmuel A Bensasson - One of the best experts on this subject based on the ideXlab platform.
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Lyn is a target gene for prostate cancer sequence based inhibition induces regression of human tumor xenografts
Cancer Research, 2004Co-Authors: Mirela Goldenbergfurmanov, Ilan Stein, Eli Pikarsky, Hila Rubin, Shafika Kasem, Marc R Wygoda, Irina Weinstein, Hadas Reuveni, Shmuel A BensassonAbstract:The Src-related Protein Kinase Lyn plays an important role in B-cell activation. However, several lines of evidence suggest that it is also involved in the control of cellular proliferation and the inhibition of apoptosis. We have discovered that Lyn is expressed in normal prostate epithelia, in 95% of primary human prostate cancer (PC) specimens examined, and in all of the PC cell lines that we assayed. Moreover, Lyn knockout mice display abnormal prostate gland morphogenesis, which suggests that Lyn plays an important role in prostate epithelium development and implies that Lyn is a candidate target for specific therapy for PC. Using a drug-design strategy to construct sequence-based peptide inhibitors, a Lyn-specific inhibitor, KRX-123, targeting a unique interaction site within Lyn, was synthesized. KRX-123 was found to inhibit cellular proliferation in three hormone-refractory PC cell lines, DU145, PC3, and TSU-Pr1 with IC(50) values of 2-4 micro M. In vivo, tumor volume of DU145 explants in nude mice was significantly reduced after once-a-week injections of KRX-123, at a dose of 10 mg/kg, for a period of 5 weeks. Histological analyses of the treated tumors indicated extensive apoptosis. Thus, we suggest that Lyn inhibition may serve as a prime target for the treatment of hormone-refractory PC.
Tessandra Stewart - One of the best experts on this subject based on the ideXlab platform.
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α synuclein a chemoattractant directs microglial migration via h2o2 dependent Lyn phosphorylation
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Shijun Wang, Chun Hsien Chu, Tessandra Stewart, Carmen Ginghina, Yifei Wang, Hui Nie, Mingri Guo, Belinda Wilson, Jaushyong Hong, Jing ZhangAbstract:Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-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 α-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 α-syn–mediated microglial migration reaches beyond Parkinson’s disease.
Jaushyong Hong - One of the best experts on this subject based on the ideXlab platform.
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α synuclein a chemoattractant directs microglial migration via h2o2 dependent Lyn phosphorylation
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Shijun Wang, Chun Hsien Chu, Tessandra Stewart, Carmen Ginghina, Yifei Wang, Hui Nie, Mingri Guo, Belinda Wilson, Jaushyong Hong, Jing ZhangAbstract:Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-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 α-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 α-syn–mediated microglial migration reaches beyond Parkinson’s disease.
