Intracellular stability of tyrosine hydroxylase regulated by proteasomal degradation of the enzyme and neurodegeneration of dopaminergic cells
| Project/Area Number |
25461296
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OTA Akira 藤田保健衛生大学, 医学部, 名誉教授 (10247637)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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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| Keywords | チロシン水酸化酵素 / プロテアソーム分解 / 14-3-3プロテイン / リン酸化 |
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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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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Aripiprazole increases NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1 in PC12 cells.2014
Author(s)
Yoko S Kaneko, Takeshi Takayanagi, Hiroshi Nagasaki, Yu Kodani, Akira Nakashima, Keiji Mori, Atsushi Suzuki, Mitsuyasu Itoh, Kazunao Kondo, Toshiharu Nagatsu, Miyuki Ota and Akira Ota.
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Journal Title
J Neural Transm
Volume: Epub ahead of print
Related Report
Peer Reviewed
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