| Project/Area Number |
16H05151
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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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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
KAKIZUKA Akira 京都大学, 生命科学研究科, 教授 (80204329)
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| Research Collaborator |
IMAMURA Hiromi
SASAOKA Norio
SUGIYAMA Yuma
NAKANO Masaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | VCP/p97 / ATP制御 / 神経細胞死 / 飢餓 / 恒常性維持 / パーキンソン病 / 心筋梗塞 / 脳梗塞 / VCP / ATPase / 栄養飢餓 / ATP / 恒常性維持機構 / 新規機能 / 創薬基盤 / 飢餓応答 / 細胞死 / 疾患治療 / 細菌 / 蛋白質 / ストレス |
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| Outline of Final Research Achievements |
Humans are said to perform the synthesis and degradation of ATP equivalent to their weight per day, and ATP and ATPase are essential for the activity of the organism. Among the soluble ATPases, VCP is the most abundant but its function is not well understood. By this study, it has been shown that VCP forms unique structures in cells when starved and contributes to the avoidance of cell death. In addition, intervention experiments of KUSs (inhibitors of the ATPase activity of VCP that we developed) in model animals of Parkinson disease, myocardial infarction, and cerebral infarction, indicated that KUSs had the effects of improving the disease states of these disorders.
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| Academic Significance and Societal Importance of the Research Achievements |
生物の生存にとって最大の脅威の1つが飢餓であるが、飢餓に対して細胞がどのような対応を行っているかはよく解っていなかった。本研究によって、細胞内で重要な働きをするVCPと呼ばれる主要なATPaseが、飢餓時に細胞内での局在を変化させることで、自身のATPase活性を抑制し、飢餓時の細胞死を回避していることが明らかになった。一方、パーキンソン病、心筋梗塞、脳梗塞に対し、このVCPのATPase活性を抑制する薬剤の投与が、有効な治療に繋がる可能性を動物実験で示すことができた。
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