Drug discovery and research for regulation of chronic inflammation caused by microglial activation
| Project/Area Number |
17K17947
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
Neurochemistry/Neuropharmacology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Research Collaborator |
TSUDA Makoto
SAITOH Hidetoshi
Jose Caaveiro
INOUE Kazuhide
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ミクログリア / 医薬品探索 / サイトカイン / ATP受容体 / 慢性炎症 / P2X7受容体 / IL-1β / アカデミア創薬 / ドラッグリポジショニング |
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| Outline of Final Research Achievements |
The excess production and release of inflammatory factors from microglial cells are involved in the development and maintenance of central nervous system inflammation. Therefore, in this study, we aimed to search for compounds to regulate microglia-mediated inflammation among approved drugs libraries by high-throughput screening (HTS). We found that some compounds inhibit not only the function of P2X7R but also the release of IL-1β from microglial cells. Moreover, we succeeded that intrathecal administration of a potent compound among them produced a reversal of nerve injury-induced mechanical allodynia in a rat model of neuropathic pain. In addition, we also succeeded that a compound, which suppresses the production and release of IL-1β from microglial cells, recovered depressive-like behavior caused by chronic inflammation. These results suggest that approved drugs discovered by HTS may be able to regulate microglia-mediated inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
現代の医薬品開発において、創薬ターゲットの枯渇が問題視されている中、安全性に関する適正な情報を有する既存薬の中から中枢のミクログリアに新たな薬効を示す化合物を見出すことを目的とした本研究は、画期的な治療戦略法となり得る。本研究成果からミクログリアを標的とした革新的な中枢疾患系疾患の治療薬につながることが期待でき、学術的意義および社会的意義は高いと考えられる。
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Report
(3 results)
Research Products
(10 results)
