| Project/Area Number |
18H02611
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Juntendo University (2019-2020)
Niigata University (2018) |
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Principal Investigator |
Komatsu Masaaki 順天堂大学, 医学(系)研究科(研究院), 教授 (90356254)
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| Co-Investigator(Kenkyū-buntansha) |
大江 知之 慶應義塾大学, 薬学部(芝共立), 准教授 (30624283)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | オートファジー / 選択的オートファジー / Nrf2 / LC3 / Keap1 / オートファジープローブ / 低分子化合物 / プローブ / p62 / 化合物 |
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| Outline of Final Research Achievements |
On the basis of this research project, we have succeeded for the first time in developing selective autophagy inhibitory mice. This genetic modified mouse will be a powerful tool for autophagy research, including the physiological significance of selective autophagy, and the screening of novel autophagy substrates. We have also developed a potent Nrf2 activator, KMN003, based on molecular mechanisms and confirmed its efficacy in vivo. Since Nrf2 activators are potential therapeutic agents for multiple sclerosis and diabetic nephropathy, we expect to verify their efficacy using these pathological mouse models.
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| Academic Significance and Societal Importance of the Research Achievements |
世界初の選択的オートファジー阻害マウスの開発に成功した。また、強力なNrf2活性化剤KMN003を開発し、マウス生体内においてもその効果を確かめた。オートファジー、Nrf2ともに神経変性疾患やがん等の重篤疾患の発症予防に中心的な役割を持つことが分かっており、本研究により開発されたマウスや低分子化合物が、基礎研究のみならずヒト疾患発症機構の解明や予防機序の解明に役立つことが期待される。
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