| Project/Area Number |
16K15317
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平田 佳之 大阪薬科大学, 薬学部, 助教 (00745854)
長岡 康夫 関西大学, 化学生命工学部, 教授 (90243039)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | PPI阻害剤 / p53 / MDM2 / MDMX / 神経細胞 / 血管内皮 / 血管内皮細胞 / 血液脳関門 / 蛋白相互作用阻害剤 / 神経保護剤 / 低分子化合物 / 脳虚血 / パーキンソン病 / 脳神経疾患 / 蛋白質 / 蛋白蛋白相互作用 / 創薬化学 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
Protein-protein interactions (PPI) are fundamental to cell biological processes and are often dysregulated in various neurological disorders. PPI hence represent a huge class of therapeutic targets and modulation of PPI with small molecules has becoming increasingly important in drug discovery. To screen for novel neuroprotective small-molecule PPI inhibitors in in vitro and in vivo Parkinson’s disease (PD) and stroke. PPI inhibitors, with protective effects against MPP+-induced neuronal death in in vitro model were identified. Furthermore, oral administration of PPI inhibitors before MPTP mitigated MPTP-induced loss of dopaminergic neurons in substantia nigra, compared with saline-treated control mice. Also, PPI inhibitors mitigated ischemic stroke, resulting in enhanced functional outcome. The discovery of these small-molecule p53/negative regulator-interaction inhibitors with neuroprotective properties may pave the way to new therapeutic strategies for PD or stroke treatment.
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