| Project/Area Number |
18K06588
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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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| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
水野 美麗 昭和大学, 薬学部, 助教 (60766195)
大野 彰子 国立医薬品食品衛生研究所, 安全性予測評価部, 主任研究官 (70356236)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | アルツハイマー病 / アミロイドβ / カテキン / プロシアニジン / フィセチン / アミロイド |
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| Outline of Final Research Achievements |
Natural catechins and their polymeric compounds inhibit amyloid-β aggregation and oxidative stress, which are the causes of Alzheimer's disease. In this study, we modified the structures of these compounds in order to develop more potent compounds. When methyl groups were introduced into catechin and fisetin, the antioxidant activity increased dramatically. When the geometry of one or both catechin molecules in catechin dimer were constrained to be planar, potent neuroprotective effects against amyloid-β-induced cytotoxicity as well as strong antioxidative activities were was observed.
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| Academic Significance and Societal Importance of the Research Achievements |
認知症の原因の約7割を占め、40代から60代の若年性の患者も急増しているアルツハイマー病は、未だ有効な治療法が確立されていない。市販されている医薬品はダメージを受けた神経を賦活化させる作用はあるが、発症を抑えることはできない。研究で設計・合成した化合物は安全性の高い天然カテキンの誘導体であり、アルツハイマー病発症の初期の段階に作用して神経毒性を抑制することから、根本的な予防・治療薬の開発につながる。
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