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KMID : 0624620200530100527
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BMB Reports
2020 Volume.53 No. 10 p.527 ~ p.532
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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
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Yang Seung-Ju
Han A-Reum
Choi Hye-Rim
Hwang Kyouk
Kim Eun-A
Choi Soo-Young
Cho Sung-Woo
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Abstract
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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.
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KEYWORD
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Autophagy, Cortical neurons, Glutamate, N-adamantyl-4-methylthiazol-2-amine, Neurotoxicity
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