2021 Fiscal Year Final Research Report
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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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 |
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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Free Research Field |
脳神経内科学、神経遺伝学
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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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