Elucidation of pathogenesis and development of treatment for spinocerebellar ataxia due to a non-coding microsatellite repeat expansion
| Project/Area Number |
16K09665
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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 |
Neurology
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| Research Institution | Gunma University |
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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) |
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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 / マイクロサテライト・リピート / RNA foci / RAN translation / SCA8 / 病態修飾治療 |
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| 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.
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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。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome2018
Author(s)
Yabe I, Yaguchi H, Kato Y, Miki Y, Takahashi H, Tanikawa S, Shirai S, Takahashi I, Kimura M, Hama Y, Matsushima M, Fujioka S, Kano T, Watanabe M, Nakagawa S, Kunieda Y, Ikeda Y, Hasegawa M, Nishihara H, Ohtsuka T, Tanaka S, Tsuboi Y, Hatakeyama S, Wakabayashi K, Sasaki H
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 819-819
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts.2017
Author(s)
Iwama K, Mizuguchi T, Takanashi JI, Shibayama H, Shichiji M, Ito S, Oguni H, Yamamoto T, Sekine A, Nagamine S, Ikeda Y, Nishida H, Kumada S, Yoshida T, Awaya T, Tanaka R, Chikuchi R, Niwa H, Oka YI, Miyatake S, Nakashima M, Takata A, Miyake N, Ito S, Saitsu H, Matsumoto N.
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Journal Title
Clinical Genetics
Volume: -
Issue: 2
Pages: 180-187
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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