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Article

Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway

College of Pharmacy, Keimyung University, Daegu 42601, Korea
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Author to whom correspondence should be addressed.
Academic Editor: Elena Goncharova
Int. J. Mol. Sci. 2021, 22(5), 2274; https://doi.org/10.3390/ijms22052274
Received: 10 January 2021 / Revised: 13 February 2021 / Accepted: 22 February 2021 / Published: 25 February 2021
(This article belongs to the Special Issue mTOR Signaling Network in Cell Biology and Human Disease)
Methamphetamine (METH) is a highly addictive drug that induces irreversible damage to neuronal cells and pathological malfunction in the brain. Aromadendrin, isolated from the flowers of Chionanthus retusus, has been shown to have anti-inflammatory or anti-tumor activity. Nevertheless, it has been reported that METH exacerbates neurotoxicity by inducing endoplasmic reticulum (ER) stress via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in neuronal cells. There is little evidence that aromadendrin protects cells from neurotoxicity induced by METH. In this study, we found that aromadendrin partially suppressed the METH-induced cell death in SH-SY5y cells without causing cytotoxicity. Aromadendrin regulated METH-induced ER stress by preserving the phosphorylation of the PI3K/Akt/mTOR signaling pathway in METH-exposed SH-SY5y cells. In addition, aromadendrin mitigated METH-induced autophagic and the apoptotic pathways in METH-exposed SH-SY5y cells. Mechanistic studies revealed that pre-treatment with aromadendrin restored the expression of anti-apoptotic proteins in METH-exposed conditions. The inhibitor assay confirmed that aromadendrin-mediated restoration of mTOR phosphorylation protected cells from autophagy and apoptosis in METH-exposed cells. Therefore, these findings suggest that aromadendrin relatively has a protective effect on SH-SY5y cells against autophagy and apoptosis induced by METH via regulation of ER stress and the PI3K/Akt/mTOR signaling pathway. View Full-Text
Keywords: METH; aromadendrin; neurotoxicity; SH-SY5y cells; protection; mTOR signaling METH; aromadendrin; neurotoxicity; SH-SY5y cells; protection; mTOR signaling
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MDPI and ACS Style

Lee, H.-S.; Kim, E.-N.; Jeong, G.-S. Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway. Int. J. Mol. Sci. 2021, 22, 2274. https://doi.org/10.3390/ijms22052274

AMA Style

Lee H-S, Kim E-N, Jeong G-S. Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway. International Journal of Molecular Sciences. 2021; 22(5):2274. https://doi.org/10.3390/ijms22052274

Chicago/Turabian Style

Lee, Hyun-Su, Eun-Nam Kim, and Gil-Saeng Jeong. 2021. "Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway" International Journal of Molecular Sciences 22, no. 5: 2274. https://doi.org/10.3390/ijms22052274

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