Development of a new therapy for L-dopa-induced dyskinesia in Parkinson's disease targeting nuclear factor kappa b

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokushima
• Principal Investigator: MORIGAKI Ryoma 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (70710565)
• Co-Investigator(Renkei-kenkyūsha): KAJI Ryuji 徳島大学, 大学院医歯薬学研究部, 教授 (00214304)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

不随意運動症