論文

査読有り 国際誌
2021年12月

Age-related demethylation of the TDP-43 autoregulatory region in the human motor cortex

Communications Biology
  • Yuka Koike
  • Akihiro Sugai
  • Norikazu Hara
  • Junko Ito
  • Akio Yokoseki
  • Tomohiko Ishihara
  • Takuma Yamagishi
  • Shintaro Tsuboguchi
  • Mari Tada
  • Takeshi Ikeuchi
  • Akiyoshi Kakita
  • Osamu Onodera
  • 全て表示

4
1
開始ページ
1107
終了ページ
1107
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s42003-021-02621-0
出版者・発行元
Springer Science and Business Media LLC

Abstract

In amyotrophic lateral sclerosis (ALS), TAR DNA-binding protein 43 (TDP-43), which is encoded by TARDBP, forms aggregates in the motor cortex. This aggregate formation may be triggered by an increase in the TDP-43 level with aging. However, the amount of TDP-43 is autoregulated by alternative splicing of the TARDBP 3′UTR, and how this autoregulation is affected by aging remains to be elucidated. We found that DNA demethylation in the autoregulatory region in the TARDBP 3′UTR reduced alternative splicing and increased TARDBP mRNA expression. Furthermore, in the human motor cortex, we found that this region was demethylated with aging, resulting in increased expression of TARDBP mRNA. The acceleration of DNA demethylation in the motor cortex was associated with the age of ALS onset. In summary, the dysregulation of TDP-43 autoregulation by age-related DNA demethylation in the motor cortex may explain the contribution of aging and motor system selectivity in ALS.

リンク情報
DOI
https://doi.org/10.1038/s42003-021-02621-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34548609
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455575
URL
https://www.nature.com/articles/s42003-021-02621-0.pdf
URL
https://www.nature.com/articles/s42003-021-02621-0
ID情報
  • DOI : 10.1038/s42003-021-02621-0
  • eISSN : 2399-3642
  • PubMed ID : 34548609
  • PubMed Central 記事ID : PMC8455575

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