Elucidation of the pathogenic mechanisms of ALS/FTLD by identifying molecules related to repeat-associated non-ATG translation

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka University (2016-2018); National Center of Neurology and Psychiatry (2015)
• Principal Investigator: Ueyama Morio 大阪大学, 医学系研究科, 特任助教 (20386593)
• Project Period (FY): 2015-04-01 – 2019-03-31
• 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

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.

Free Research Field

神経分子病態

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。