Analysis of the role of ceramide kinase in dyslipidemia and its application to drug discovery
| Project/Area Number |
17K08303
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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 |
Pharmacology in pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | セラミドキナーゼ / セラミド-1-リン酸 / 脂質代謝異常症 / グリア細胞 / 脱髄 / オートファジー |
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| Outline of Final Research Achievements |
The dyslipidemia focused in this study is an intractable disease in which cholesterol and sphingolipids accumulate in cells and cause central nervous system disorders (particularly, Purkinje cell loss). In this study, we analyzed the role of ceramide kinase in dyslipidemia using cell, mouse, disease-specific iPS cells. The results showed that inhibition of ceramide kinase suppressed the onset of dyslipidemia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で着目している脂質代謝異常症は遺伝病であるため、根本的な治療には遺伝子治療が必要である。しかしながら、遺伝子治療の実用化は容易ではない。本研究により脂質蓄積症の病態発症機構の一端が明らかになり、さらに、セラミドキナーゼが創薬標的となることが明らかになった。今後、新規セラミドキナーゼ阻害剤を開発することで、本病態の革新的治療薬を創出できる可能性がある。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Inhibitory effects of ceramide kinase on Rac1 activation, lamellipodium formation, cell migration, and metastasis of A549 lung cancer cells2020
Author(s)
Tomizawa S, Tamori M, Tanaka A, Utsumi N, Sato H, Hatakeyama H, Hisaka A, Kohama T, Yamagata K, Honda T, Nakamura H, Murayama T
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Journal Title
Biochim Biophys Acta Mol Cell Biol Lipids
Volume: 1865
Issue: 6
Pages: 158675-158675
DOI
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Peer Reviewed
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[Journal Article] Cellular density-dependent increases in HIF-1α compete with c-Myc to down-regulate human EP4 receptor promoter activity through Sp-1-binding region2018
Author(s)
Seira N, Yamagata K, Fukushima K, Araki Y, Kurata N, Yanagisawa N, Mashimo M, Nakamura H, Regan JW, Murayama T, Fujino H
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Journal Title
Pharmacol Res Perspect
Volume: 6
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] HIF-1α and c-Myc oppositely regulate human EP4 receptor promoter activity in human colon cancer HCA-7 cells2019
Author(s)
山形 一行, 清良 尚史, 福島 圭穣, 荒木 裕美, 倉田 直希, 柳澤 直樹, 間下 雅士, 中村 浩之, REGAN W. John, 村山 俊彦, 藤野 裕道
Organizer
第92回日本薬理学会年会
Related Report
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[Presentation] Hypoxia inducible factor-1α regulates human EP4 receptor expression by binding to specificity protein-12018
Author(s)
Seira N, Yamagata K, Fukushima K, Araki Y, Kurata N, Yanagisawa N, Mashimo M, Nakamura H, Regan J.W, Murayama T, Fujino H
Organizer
The 3rd Joint Seminar between Faculty of Pharmacy, Mahidol University and Graduate School of Pharmaceutical Sciences, Chiba University
Related Report
Int'l Joint Research
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