| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Research Abstract |
Molecular mechanisms of Parkinson’s disease pathogenesis were analyzed by functional analyses of DJ-1 protein, the product of protooncogene DJ-1, also identified as PARK7, a responsible gene for familial Parkinson’s disease. We revealed that DJ-1 transactivated key enzymes for dopamine biosynthesis, specifically bound to a dopamine transporter VMAT-2, transactivation of Nrf2-dependent anti-oxidative stress genes via specific binding and inhibition of PTEN, and was required for neurite formation in cooperation with Drebrin, an actin-binding protein. As for drug development, several low-molecular chemicals specifically bound to DJ-1 prohibited hyperoxidation of the protein and preserved a variety of physiological activities of DJ-1 under oxidative stress conditions. The chemicals were thus suggested to be promising candidates for preventive and curative drug for Parkinson’s disease.
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