Elucidation of pathogenesis and development of treatment for spinocerebellar ataxia due to a non-coding microsatellite repeat expansion

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• 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): 2016-04-01 – 2019-03-31
• Keywords: 脊髄小脳変性症 / 脊髄小脳失調症 / マイクロサテライトリピート / リピート伸長変異 / siRNA / SCA36

Outline of Final Research Achievements

We developed a cell culture model for spinocerebellar ataxia type 36 (SCA36), which is caused by a GGCCTG repeat expansion mutation located in the untranslated region of the causative gene. This model reproduced the RNA foci or the repeat-associated non-ATG translation (RANT)-associated proteins, which are associated to cell death. When siRNAs against the transcriptional elongation factor yeast Spt4/Spt5 orthologues were introduced to the SCA36 cell culture model, it was revealed that the cytotoxicity is reduced through the suppression of expression of (GGCCUG)exp transcripts through Spt4/Spt5 silencing.

Free Research Field

脳神経内科学

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確立し、これを用いてSpt4/Spt5に対するsiRNAによる細胞毒性減少効果を明らかにした。本研究による成果はSCA36に対する治療法を今後開発する上での重要な基礎データになると考えられた。