| 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 |
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| Research Field |
Applied pharmacology
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| Research Institution | Tohoku University |
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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 |
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| 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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