Elucidation of the pathogenic mechanisms of ALS/FTLD by identifying molecules related to repeat-associated non-ATG translation
| Project/Area Number |
15K09331
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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 | Osaka University (2016-2018)
National Center of Neurology and Psychiatry (2015) |
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Principal Investigator |
Ueyama Morio 大阪大学, 医学系研究科, 特任助教 (20386593)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 筋萎縮性側索硬化症 / 前頭側頭葉変性症 / リピート関連非ATG翻訳 / 異常伸長リピート / RNAリピート病 / 異常伸長リピートRNA / ショウジョウバエ |
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| Outline of Final Research Achievements |
Among the intractable neurodegenerative diseases, amyotrophic lateral sclerosis(ALS) and frontotemporal lobar degeneration(FTLD), the mutation of C9ORF72 gene is the most common mutation in ALS/FTLD(C9ALS/FTLD). The toxicity of proteins produced by repeat-associated non-ATG(RAN) translation is though to be associated with pathogenesis of C9ALS/FTLD. Decreasing this toxicity by regulating RAN translation leads to one of the novel therapy. We identified suppressive modifier(s) of RAN translation by genetic analysis using Drosophila model for ALS/FTLD related to mutation of C9ORF72 gene.
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| Academic Significance and Societal Importance of the Research Achievements |
根治療法が未だにない筋萎縮性側索硬化症と前頭側頭葉変性症に対して、リピート関連非ATG(RAN)翻訳により産生されるタンパク質の毒性を減少させ、発症を抑制することができる因子を発見した。この抑制因子を利用することで新たな治療法開発が進展すると考えられる。同時にこれまで一般的に考えられてた開始コドンATGに依存する翻訳ではない、RAN翻訳のメカニズムの一端を明らかにする研究でもある。
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Report
(5 results)
Research Products
(31 results)
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[Journal Article] Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS.2018
Author(s)
Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M.
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Journal Title
Exp Cell Res.
Volume: 371
Issue: 2
Pages: 311-321
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2018
Author(s)
Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
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Journal Title
Hum Mol Genet.
Volume: 27
Issue: 5
Pages: 823-836
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Regulatory Role of RNA Chaperone TDP-43 for RNA Misfolding and Repeat-Associated Translation in SCA312017
Author(s)
Taro Ishiguro, Nozomu Sato, Morio Ueyama, Nobuhiro Fujikake, Chantal Sellier, Akemi Kanegami, Eiichi Tokuda, Bita Zamiri, Terence Gall-Duncan, Mila Mirceta, Yoshiaki Furukawa, 他８名
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Journal Title
Neuron
Volume: 94
Issue: 1
Pages: 108-124
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] p62 plays a protective role in the autophagic degradation of polyglutamine protein oligomers in polyglutamine disease model flies.2015
Author(s)
Saitoh Y, Fujikake N, Okamoto Y, Popiel HA, Hatanaka Y, Ueyama M, Suzuki M, Gaumer S, Murata M, Wada K, Nagai Y.
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Journal Title
J Biol Chem
Volume: 290
Issue: 3
Pages: 1442-53
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Toxicity of dipeptide repeat proteins in C9 ALS/FTD model fly2016
Author(s)
M. Ueyama, T. Ishiguro, T. F. Gendron, N. Fujikake, T. Konno, A. Koyama, O. Onodera, K. Ishikawa, K. Wada, L. Petrucelli, Y. Nagai
Organizer
11th Brain Research Conference
Place of Presentation
Paradise Point, San Diego (U.S.A.)
Year and Date
2016-11-10
Related Report
Int'l Joint Research
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