Analysis of a new mechanism to specifically inhibit amyloid-beta protein production
| Project/Area Number |
18K14883
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Nagoya University (2020-2021)
Shiga University of Medical Science (2018-2019) |
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Principal Investigator |
Hibino Emi 名古屋大学, 大学院創薬科学研究科, 特任助教 (00803371)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | アルツハイマー病 / プレセニリン-1 / FAM3C / ILEI / NMR / γセクレターゼ / SBDD / 溶液NMR / 構造―機能連関 / タンパク質間相互作用 / Alaスキャニング / 計算科学 |
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| Outline of Final Research Achievements |
Alzheimer's disease is associated with the accumulation of amyloid-β protein (Aβ) in the brain. The secreted protein ILEI has been reported to inhibit the production of Aβ and APP-CTF, a precursor of Aβ. In this study, I first established a simple evaluation system for the Alzheimer's disease-preventive function of ILEI using cultured cells, and then used the evaluation system to identify the site that appears to be the active center of ILEI. Although ILEI is also known to cause oncogenesis, this study strongly suggests that the active centers of ILEI's inhibitory and oncogenic effects on Aβ production are separate. The results of this research will provide the foundation for the development of therapeutic and preventive drugs for Alzheimer's disease.
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| Academic Significance and Societal Importance of the Research Achievements |
近年開発されたアルツハイマー病治療薬は承認が見送られるなど、その開発は非常に難航している。ILEIは、全く新しい機構でAβ産生を抑制する。治療ターゲットとして着目されたγセクレターゼ阻害薬では、Notchシグナルの抑制により重大な副作用が見られたが、ILEIにおいてはNotchシグナル抑制を呈さないことから、期待される分子である。しかしながらILEIはがん化促進作用を有するため、ILEIそのものの標的化は多大なるリスクを伴う。本研究では、この両極端の面が分割可能であることを示すことができた。
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Report
(5 results)
Research Products
(12 results)
