Therapeutic development of microsatellite repeat expansion disorder focusing on the transcriptional mechanism
Project/Area Number |
19K07813
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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Research Institution | Gunma University |
Principal Investigator |
Ikeda Yoshio 群馬大学, 大学院医学系研究科, 教授 (00282400)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 脊髄小脳変性症 / 脊髄小脳失調症 / グアニン四重鎖 / ポルフィリン / マイクロサテライトリピート / RNA gain-of-function / RAN translation / 培養細胞モデル |
Outline of Research at the Start |
これまでの我々の研究において、脊髄小脳失調症36型(SCA36)における非翻訳領域GGCCTGリピート伸長変異、およびc9orf72連鎖性筋萎縮性側索硬化症/前頭側頭型認知症(c9-ALS/FTD)におけるGGGGCCリピート伸長変異を導入し、これらの疾患の病態を反映する培養細胞モデルの作成を行った。本研究においては、これらの培養細胞モデルに加えて、商業目的で購入・利用が可能な各種のマイクロサテライトリピート伸長病患者由来の線維芽細胞を対象とし、これらの疾患の病態解明および治療開発を目指して様々な検討を順次遂行していく。
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Outline of Final Research Achievements |
To clarify molecular pathogenesis of spinocerebellar ataxia type 36 (SCA36), the role of aggregates (RNA foci) or G-quadruplex (GQ) formed by the expanded GGCCUG repeat transcripts were investigated by using SCA36 cell culture model. Various porphyrin derivatives were examined as a candidate chemical compound to treat SCA36 by stabilizing the SCA36 GQ structure, and inhibiting downstream events. As a result, some of porphyrin derivatives could suppress SCA36 RNA foci formation and its cytotoxicity, and improve cell viability. These data were considered to be important for developing treatments for SCA36.
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Academic Significance and Societal Importance of the Research Achievements |
脊髄小脳失調症36型(SCA36)の病態を再現する培養細胞モデルを用いて、RNAレベルの病態に関与するGGCCTGリピート伸長変異に由来する転写物の凝集体(RNA foci)やグアニン四重鎖(G-quadruplex:GQ)の病態への関与を明らかにした。また、複数のポルフィリン誘導体の病態改善効果を明らかにした。本研究による成果はSCA36に対する治療法を開発する上での重要な基礎データになると考えられた。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Deep White Matter Lesions Are Associated with Early Recognition of Dementia in Alzheimer's Disease.2019
Author(s)
Kasahara H, Ikeda M, Nagashima K, Fujita Y, Makioka K, Tsukagoshi S, Yamazaki T, Takai E, Sanada E, Kobayashi A, Kishi K, Suto T, Higuchi T, Tsushima Y, Ikeda Y
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Journal Title
Journal of Alzheimer's Disease
Volume: 68
Issue: 2
Pages: 797-808
DOI
Related Report
Peer Reviewed / Open Access
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