Modeling ALS with TDP-43 proteinopathy

2016 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

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