Modeling ALS with TDP-43 proteinopathy

Research Project

Project/Area Number	15H06225
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Neurology
Research Institution	Niigata University
Principal Investigator	Sugai Akihiro 新潟大学, 医歯学総合病院, 特任助教 (70758903)
Project Period (FY)	2015-08-28 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	ALS / TDP-43 / アンチセンスオリゴ / 自己制御機構 / マウスモデル / iPS細胞モデル / 選択的スプライシング / RNA代謝 / 病態モデル / 筋萎縮性側索硬化症 / スプライシング / アンチセンス核酸
Outline of Final Research Achievements	Accumulation of TDP-43 in the cytoplasm of motor neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS). TDP-43 regulates its own mRNA expression. We recently elucidated that a redundant transcription followed by alternative splicing of the pre-mRNA is a critical process for the auto-regulation and that TDP-43 mRNA is increased in ALS motor neurons. Based on this finding, we disturbed the alternative spicing and developed a model with increased intrinsic TDP-43 in mice spinal cords and in human iPS-cell derived neurons.

Report

(3 results)