Understanding of the mechanism of ribitol-phosphate modification and application of its physiological function to therapy
| Project/Area Number |
18H02616
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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 | Ehime University (2020)
Kobe University (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
萬谷 博 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (20321870)
田村 純一 鳥取大学, 農学部, 教授 (30221401)
片野坂 友紀 岡山大学, 医歯薬学総合研究科, 講師 (60432639)
山口 芳樹 東北医科薬科大学, 薬学部, 教授 (90323451)
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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 |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 糖鎖 / 筋ジストロフィー / 疾患モデル / ジストログリカン / リビトールリン酸 / フクチン |
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| Outline of Final Research Achievements |
Ribitol-phosphate is a novel post-translational moiety that we identified and its abnormal modification results in muscular dystrophy and mental retardation. However, it was unknown how defects in ribitol-phosphate modification lead to tissue dysfunction and human diseases. In this study, using ribitol-phosphate-deficient mice we showed that the degree of ribitol-phosphate modification during fetal stage is related to pathological severity in brain and that ribitol-phosphate modification plays important roles in function of cardiac muscle cells and the maintenance of cytoskeletons. Based on these findings, we proposed therapeutic strategies to muscular dystrophy.
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| Academic Significance and Societal Importance of the Research Achievements |
リビトールリン酸修飾異常症の病態分子機構に不明な点は多く、有効な治療法も存在しない。本研究では、作出したリビトールリン酸不全マウスの病態解析をすすめ、リビトールリン酸修飾の不全から病的表現型に至る発症メカニズムを解明できた。更に、発症メカニズムに基づいた治療戦略の提唱にも至った。これらの成果は、疾患機序の解明や治療法の開発につながり、学術的・社会的にも大きな貢献を果たした。
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Lactone-Driven Ester-to-Amide Derivatization for Sialic Acid Linkage-Specific Alkylamidation2020
Author(s)
Jun-Ichi Furukawa 1, Hisatoshi Hanamatsu 2, Takashi Nishikaze 3, Hiroshi Manya 4, Nobuaki Miura 5, Hirokazu Yagi 6, Ikuko Yokota 1, Keiko Akasaka-Manya 4, Tamao Endo 4, Motoi Kanagawa 7 8, Norimasa Iwasaki 1, Koichi Tanaka 3
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Journal Title
Anal Chem .
Volume: 3
Issue: 21
Pages: 14383-14392
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy.2020
Author(s)
Kuwabara N, Imae R, Manya H, Tanaka T, Mizuno M, Tsumoto H, Kanagawa M, Kobayashi K, Toda T, Senda T, Endo T, Kato R.
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Journal Title
Nat Commun.
Volume: 11
Issue: 1
Pages: 303-303
DOI
Related Report
Peer Reviewed / Open Access
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