論文

査読有り 国際誌
2019年

Inhibition of the glutamine transporter SNAT1 confers neuroprotection in mice by modulating the mTOR-autophagy system.

Communications biology
  • Daisuke Yamada
  • Kenji Kawabe
  • Ikue Tosa
  • Shunpei Tsukamoto
  • Ryota Nakazato
  • Miki Kou
  • Koichi Fujikawa
  • Saki Nakamura
  • Mitsuaki Ono
  • Toshitaka Oohashi
  • Mari Kaneko
  • Shioi Go
  • Eiichi Hinoi
  • Yukio Yoneda
  • Takeshi Takarada
  • 全て表示

2
開始ページ
346
終了ページ
346
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s42003-019-0582-4

The pathophysiological role of mammalian target of rapamycin complex 1 (mTORC1) in neurodegenerative diseases is established, but possible therapeutic targets responsible for its activation in neurons must be explored. Here we identified solute carrier family 38a member 1 (SNAT1, Slc38a1) as a positive regulator of mTORC1 in neurons. Slc38a1
flox/flox
and Synapsin I-Cre mice were crossed to generate mutant mice in which Slc38a1 was selectively deleted in neurons. Measurement of 2,3,5-triphenyltetrazolium chloride (TTC) or the MAP2-negative area in a mouse model of middle cerebral artery occlusion (MCAO) revealed that Slc38a1 deficiency decreased infarct size. We found a transient increase in the phosphorylation of p70S6k1 (pp70S6k1) and a suppressive effect of rapamycin on infarct size in MCAO mice. Autophagy inhibitors completely mitigated the suppressive effect of SNAT1 deficiency on neuronal cell death under in vitro stroke culture conditions. These results demonstrate that SNAT1 promoted ischemic brain damage via mTOR-autophagy system.

リンク情報
DOI
https://doi.org/10.1038/s42003-019-0582-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31552299
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751179
ID情報
  • DOI : 10.1038/s42003-019-0582-4
  • PubMed ID : 31552299
  • PubMed Central 記事ID : PMC6751179

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