Dock family proteins in neurodegeneration
| Project/Area Number |
23300138
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
NAMEKATA Kazuhiko 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 副参事研究員 (70392355)
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| Co-Investigator(Renkei-kenkyūsha) |
GUO Xiaoli 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 主任研究員 (50443114)
KIMURA Atsuko 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 主任研究員 (60569143)
WATANABE Hayaki 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (70595587)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | Dock3 / 緑内障 / 神経保護 / 神経変性疾患 / 視神経再生 / Dockファミリー / 細胞死 / アクチン / 微小管 / アルツハイマー病 / 多発性硬化症 / 軸索再生 / アクチン骨格 / GEF |
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| Research Abstract |
Dock3 is a guanine nucleotide exchange factors for the small GTPase Rac1. We found that Dock3 directly binds to NR2B, an N-methyl-D-aspartate (NMDA) receptor subunit. In transgenic mice overexpressing Dock3 (Dock3 Tg), NR2B expression in the retina was significantly decreased and NMDA-induced retinal degeneration was ameliorated. In addition, overexpression of Dock3 protected retinal ganglion cells (RGCs) from oxidative stress. We previously reported that RGC degeneration due to glutamate neurotoxicity and oxidative stress is observed in GLAST-deficient (KO) mice. In GLAST KO mice, the NR2B phosphorylation rate in the retina was significantly higher compared with Dock3 Tg:GLAST KO mice. Consistently, glaucomatous retinal degeneration was significantly improved in GLAST KO:Dock3 Tg mice compared with GLAST KO mice. These results suggest that Dock3 overexpression prevents glaucomatous retinal degeneration by suppressing both NR2B-mediated glutamate neurotoxicity and oxidative stress.
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury2013
Author(s)
Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T
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Journal Title
Cell Death and Differentiation
Volume: 20
Pages: 270-280
Related Report
Peer Reviewed
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[Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury.2013
Author(s)
Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T.
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Journal Title
Cell Death Differ.
Volume: 20
Issue: 2
Pages: 270-280
DOI
Related Report
Peer Reviewed
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[Book] ASK1-p38 経路の阻害は視神経外傷後の神経細胞死を抑制する 日本眼科学会雑誌2013
Author(s)
香留 崇, 行方和彦, 郭 暁麗, 仙波賢太郎, 橘高大二, 川村和人, 木村敦子, 原田知加子, 一條秀憲, 三田村佳典, 原田高幸
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[Book] TLR-ASK1-p38経路による神経炎症と脱髄症状の制御 日本眼科学会会誌2011
Author(s)
郭 暁麗, 原田知加子, 行方和彦, 松沢厚, Monsterrat Camps, Hong Ji, Dominique Swinnen, Catherine Jorand-Lebrun, Mathilde Muzerelle, Pierre-Alain Vitte, Thomas Rückle, 木村敦子, 神山邦子, 松本 陽, 一條秀憲, 原田高幸
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