Therapeutic development of microsatellite repeat expansion disorder focusing on the transcriptional mechanism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Gunma University
• Principal Investigator: Ikeda Yoshio 群馬大学, 大学院医学系研究科, 教授 (00282400)
• Project Period (FY): 2019-04-01 – 2022-03-31
• 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.

Free Research Field

脳神経内科学、神経遺伝学

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。