Therapeutic application of V-1 gene-dependent mechanism to Parkinson's disease potentiating dopamine biosynthesis coupled with actin dynamics

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860389
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Tohoku University
• Principal Investigator: KAWAHATA Ichiro 東北大学, 薬学研究科(研究院), 助教 (30579743)
• Project Period (FY): 2013-04-01 – 2015-03-31
• 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

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.

Free Research Field

神経科学・応用薬理学