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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

BMB Reports 2020년 53권 10호 p.527 ~ 532
양승주, 한아름, 최혜림, Hwang Kyouk, 김은아, 최수영, 조성우,
소속 상세정보
양승주 ( Yang Seung-Ju ) - Konyang University Department of Biomedical Laboratory Science
한아름 ( Han A-Reum ) - University of Ulsan College of Medicine Department of Biochemistry and Molecular Biology
최혜림 ( Choi Hye-Rim ) - Konyang University Department of Biomedical Laboratory Science
 ( Hwang Kyouk ) - University of Ulsan College of Medicine Department of Biochemistry and Molecular Biology
김은아 ( Kim Eun-A ) - University of Ulsan College of Medicine Department of Biochemistry and Molecular Biology
최수영 ( Choi Soo-Young ) - Hallym University Department of Biomedical Science
조성우 ( Cho Sung-Woo ) - University of Ulsan College of Medicine Department of Biochemistry and Molecular Biology

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 glutamateinduced 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.

키워드

Autophagy; Cortical neurons; Glutamate; N-adamantyl-4-methylthiazol-2-amine; Neurotoxicity

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