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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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N-Adamantyl-4-methylthiazol-2-amine suppresses glutamate-induced autophagic cell death via PI3K/Akt/mTOR signaling pathways in cortical neurons

  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University) ;
  • Han, A Reum (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Choi, Hye-Rim (Department of Biomedical Laboratory Science, Konyang University) ;
  • Hwang, Kyouk (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Kim, Eun-A (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
  • Received : 2020.03.20
  • Accepted : 2020.04.20
  • Published : 2020.10.31
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Abstract

We recently reported that N-adamantyl-4-methylthiazol-2-amine (KHG26693) attenuates glutamate-induced oxidative stress and inflammation in the brain. In this study, we investigated KHG 26693 as a therapeutic agent against glutamate-induced autophagic death of cortical neurons. Treatment with KHG26693 alone did not affect the viability of cultured cortical neurons but was protective against glutamate-induced cytotoxicity in a concentration-dependent manner. KHG26693 attenuated the glutamate-induced increase in protein levels of LC3, beclin-1, and p62. Whereas glutamate decreased the phosphorylation of PI3K, Akt, and mTOR, these levels were restored by treatment with KHG26693. These results suggest that KHG26693 inhibits glutamate-induced autophagy by regulating PI3K/Akt/mTOR signaling. Finally, KHG26693 treatment also attenuated glutamate-induced increases in reactive oxygen species, glutathione, glutathione peroxidase, and superoxide dismutase levels in cortical neurons, indicating that KHG26693 also protects cortical neurons against glutamate-induced autophagy by regulating the reactive oxygen species scavenging system.

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References

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