Development of a new therapy for L-dopa-induced dyskinesia in Parkinson's disease targeting nuclear factor kappa b
| Project/Area Number |
26461272
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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 | The University of Tokushima |
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Principal Investigator |
MORIGAKI Ryoma 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (70710565)
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| Co-Investigator(Kenkyū-buntansha) |
後藤 恵 徳島大学, 大学院医歯薬学研究部(医学系), 特任教授 (50240916)
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| Co-Investigator(Renkei-kenkyūsha) |
KAJI Ryuji 徳島大学, 大学院医歯薬学研究部, 教授 (00214304)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | NFκB / リン酸化タンパク質 / 線条体 / 機能分画 / パーキンソン病 / ジスキネジア / 不随意運動症 / c-fos / motor stereotypy / 線条体機能分画 / ドパミン / 常同症 |
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| Outline of Final Research Achievements |
In mice brain, phosphorylation at serine 276 residue of NFκB (p65-pS276) expressed predominantly in the nuclei of striatal medium spiny neurons (MSNs). Dopaminergic stimuli induced dose-dependent p65-pS276 expression pattern in differential functional compartments. This finding indicated that p65-pS276 was involved in the functions associated with striatum under the control of dopamine signaling. P65-pS276 bound to DNA and enhanced transcriptional activity. This resulted in neuronal activation of MSNs as determined by c-fos mRNA expression in these neurons. The specific inhibitor of p65-pS276 successfully alleviated L-dopa-induced dyskinesia in Parkinson's disease mice model. These findings elucidated a new signaling cascade in the striatum, which was responsible for the mechanism in manifesting movement disorders. Targeting p65-pS276 might contribute to developing a new therapy for L-dopa-induced dyskinesia in Parkinson’s disease.
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Report
(4 results)
Research Products
(16 results)
