Therapeutic application of V-1 gene-dependent mechanism to Parkinson's disease potentiating dopamine biosynthesis coupled with actin dynamics
Project/Area Number |
25860389
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Applied pharmacology
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Research Institution | Tohoku University |
Principal Investigator |
KAWAHATA Ichiro 東北大学, 薬学研究科(研究院), 助教 (30579743)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | V-1遺伝子 / チロシン水酸化酵素 / 芳香族アミノ酸脱炭酸酵素 / ドーパミン / Nurr1 / アクチン重合 / RhoA / パーキンソン病 / 統合的ドーパミン生合成増強機構 / V-1依存的ネットワーク / 血清応答因子 / V-1 / tyrosine hydroxylase / dopa decarboxylase / Parkinson's disease / serum responsive factor / cofilin |
Outline of Final Research Achievements |
In this project, we demonstrated the molecular mechanism of V-1 gene to regulate the expression of DA biosynthesizing enzymes, aiming the clinical application of V-1 gene therapy. We identified that V-1 requires CP to form the complex at its 44 residue to maintain TH/AADC/Nurr1 expression. Also, V-1 coordinately potentiates RhoA/Rac1/mDia activity to accelerate actin polymerization accompanied by the augmentation of MAL/SRF-mediated transcription. We further successfully identified the CArG box in TH/AADC/Nurr1 promoter region. Finally our biochemical and immunohistochemical analysis revealed that these V-1 cascades are functional in vivo too.
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Report
(3 results)
Research Products
(5 results)
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[Presentation] V-1 maintains and augments nigrostriatal dopaminergic function through actin polymerization in vitro and in vivo2013
Author(s)
Ichiro Kawahata, Shiori Ohtaku, Yanxin Lai, Junichi Morita, Shigeki Kato, Akiko Tabuchi, Masaaki Tsuda, Kazumasa Ohashi, Kensaku Mizuno, Yasuhiko Izumi, Toshiaki Kume, Akinori Akaike, Yoshihisa Tomioka, Hiroshi Ichinose, Kazuto Kobayashi, and Tohru Yamakuni
Organizer
Neuroscience 2013
Place of Presentation
San Diego, USA
Related Report
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