| Project/Area Number |
18K06792
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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 47060:Clinical pharmacy-related
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| Research Institution | Iryo Sosei University |
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Principal Investigator |
Murata Kazuko 医療創生大学, 薬学部, 客員教授 (20137631)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 陽 医療創生大学, 薬学部, 准教授 (20458235)
田島 裕久 医療創生大学, 薬学部, 教授 (50306833)
江藤 忠洋 医療創生大学, 薬学部, 准教授 (10458234)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 小胞輸送 / ユビキチン / 高次機能 / タンパク質分解 / STAM1 / 認知症 / モデルマウス |
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| Outline of Final Research Achievements |
In Alzheimer's disease, a type of dementia, accumulation of ubiquitinated proteins is observed within nerve cells. Therefore, we investigated the involvement of the STAM1 molecule of ESCRT-0, which recognizes proteins and is involved in their transport to lysosomes and degradation, in dementia using genetically modified mice. As a result, in a memory behavior test using the Y-maze, STAM1-deficient mice showed decreased memory behavior. Furthermore, when the accumulation of amyloid-β protein in cerebral tissue was examined histochemically, it was found that the accumulation of amyloid-β protein increased with age in STAM1-deficient mice. These results suggest that STAM1-deficient mice have the potential to serve as a new dementia model mouse.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は認知症の病態解明を「小胞輸送の機能破綻」という、これまで全く予想されなかったタンパク質分解系調節因子の認知機能への関与を見出し、これまでの研究とは異なる新たな視点から行ったものであり、学術的独自性ならびに学術的意義を有する。そして、このSTAM1欠損マウスはユニークな新たな機序を有する新規認知症モデル動物として、新規認知症治療薬の開発や診断薬のスクリーニングに非常に有用なツールとなる可能性が明らかとなり、認知症の新規治療薬開発に大いに貢献することが出来、本研究の社会的意義は大きい。
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