| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Recently, abnormality of the degradation of intracellular proteins has been suspected to be a major cause of neurodegenerative diseases such as Parkinson's disease. Again, the primary pathology of Parkinson's disease is degeneration of the dopamine neuron, and then degeneration is suspect to result from by quinones derived from dopamine. In this study, we clarified that the inhibition of deubiquitinating activity enhances the proteasomal degradation of tyrosine hydroxylase (TH) and that the phosphorylation of Ser19 is a trigger for the degradation. The increased degradation of TH molecule by its phosphorylation is opposite action for its increased activity by its phosphorylation on dopamine synthesis. The study indicates that the balance of the degradation and the activity might be critical for degeneration of the dopamine neuron.
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