| Project/Area Number |
15K18384
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Tokunaga Shinji 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第五部, 流動研究員 (50644621)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | NAD代謝 / 神経変性 / 創薬 / ニコチンアミド / ケミカルバイオロジー / NAD / 軸索変性 |
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| Outline of Final Research Achievements |
Axonal degeneration (the loss of structure or function of axons) precedes the appearance of neuronal cell death and contributes to the formation of the symptoms in various neurological disorders. Recently the applicant has found some nicotinamide derivatives delays axonal degeneration. In this study, we succeeded in developing improved versions of these compounds, which exhibit ability to block axonal degeneration for longer duration than already-known axon protective compounds do. We also found that these compounds display significant neuroprotective efficacy when administered orally to an experimental axonal degeneration mouse model. Furthermore, our data show the mechanism by which nicotinamide derivatives delay axonal degeneration involve preservation of mitochondrial function.
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| Academic Significance and Societal Importance of the Research Achievements |
先行研究によってビタミンB3による神経保護効果は報告されていたが、in vivo疾患モデルあるいはワーラー変性モデルに対する神経保護効果は限定的であった。本研究はマウスの後根神経節神経細胞から伸展する軸索に対する保護活性を指標として、ニコチンアミド類縁化合物の構造活性相関を展開し、より軸索保護活性が強くin vivoモデルでの治療的効果が期待できる化合物群の開発に成功した。今後の研究進展により、神経変性疾患に対する創薬シーズの発見が期待される。
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