Elucidation of mechanism that RNA G-quadruplex aggregation and its drug discovery in neurological diseases
| Project/Area Number |
16K08265
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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 | Kumamoto University (2018)
Gifu Pharmaceutical University (2016-2017) |
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Principal Investigator |
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | グアニン四重鎖 / 神経変性疾患 / 神経細胞 / RNA-G4 構造/タンパク質複合体 / 遺伝性神経変性疾患 / 神経疾患 / DNA / RNA / RAN translation |
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| Outline of Final Research Achievements |
G-quadruplex (G4) structures are stacked nucleic acid structures that can form within G-rich DNA or RNA sequences. In the pathogenesis of neurodegenerative diseases, G4 structures are formed by guanine-rich repeats, which are transcribed, result in forms aggregates with several RNA binding proteins. In this study, we aimed to analyze the components of the RNA-G4/protein complex in the brain and to elucidate the abnormal aggregation mechanism in neurodegenerative diseases. We performed immunoprecipitation using a G4 structural recognition fragment, and identifiedsome novel G4-binding proteins and G4 formed mRNAs in mouse brain.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、神経変性疾患の病態に関与するRNA-G4構造/タンパク質複合体の神経細胞における構成成分を解析・同定した。今後、この異常凝集機構を解明することで、ALS等の神経変性疾患の病態解明に迫ることができ、新たな治療標的を提示できる。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome.2018
Author(s)
Shioda N*., Yabuki Y., Yamaguchi K., Onozato M., Li Y., Kurosawa K., Tanabe H., Okamoto N., Era T., Sugiyama H., Wada T*., Fukunaga K*.
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Journal Title
Nature Medicine.
Volume: in press
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy.2016
Author(s)
Moriguchi S, Ishizuka T, Yabuki Y, Shioda N, Sasaki Y, Tagashira H, Yawo H, Yeh JZ, Sakagami H, Narahashi T, Fukunaga K.
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Journal Title
Mol Psychiatry.
Volume: 印刷中
Issue: 2
Pages: 211-221
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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