| Project/Area Number |
15K08583
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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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| Research Field |
Applied pharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Fukunaga Kohji 東北大学, 大学院薬学研究科, 教授 (90136721)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | メマンチン / KATPチャンネル / アルツハイマー病 / KATPチャネル / AD脳糖尿病仮説 / 認知・精神機能 / Memantine / CaMキナーゼII / 認知機能 / うつ症状 / 新規アダマンタン誘導体 / memantine / Kir6.2チャネル / whole-cell patch-clamp法 / カルシウムイメージング法 / CaM kinase II |
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| Outline of Final Research Achievements |
We recently discovered a novel mechanism of memory improvement by memantine via inhibition of ATP-sensitive K+ (KATP) channels. Inhibition of Kir6.2 channel by memantine improved brain insulin signaling. These results relate to brain diabetes theory causative for Alzheimer’s disease. Therefore, we have searched the novel seed compounds among adamantane derivatives with blocking action of KATP channels. We successfully discovered novel adamantane derivative, TP-compound X targeting for KATP channels, which is more potent than memantine. In the pharmacological examination, we confirmed that TP-compound improves both cognitive deficits via Kir6.2 channel inhibition and behavioral and psychological symptoms of dementia (BPSD) such as depressive-like behaviors, anxiety-like behaviors and aggressive-like behaviors via Kir6.1 channel inhibition in mice.
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