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Int. J. Mol. Sci. 2017, 18(12), 2753;

Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways

Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea
Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea
Deptartment of Oriental Pharmacy, & Wonkwang-Oriental Medicines Research Institute, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea
Author to whom correspondence should be addressed.
Received: 11 October 2017 / Revised: 9 December 2017 / Accepted: 11 December 2017 / Published: 19 December 2017
(This article belongs to the Special Issue Neuroprotective Strategies 2017)
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Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP+)-induced cell model of PD in SH-SY5Y cells and the underlying molecular mechanisms. Sulfuretin significantly decreased MPP+-induced apoptotic cell death, accompanied by a reduction in caspase 3 activity and polyADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated MPP+-induced production of intracellular reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). Consistently, sulfuretin decreased p53 expression and the Bax/Bcl-2 ratio. Moreover, sulfuretin significantly increased the phosphorylation of Akt, GSK3β, and ERK. Pharmacological inhibitors of PI3K/Akt and ERK abolished the cytoprotective effects of sulfuretin against MPP+. An inhibitor of GSK3β mimicked sulfuretin-induced protection against MPP+. Taken together, these results suggest that sulfuretin significantly attenuates MPP+-induced neurotoxicity through Akt/GSK3β and ERK signaling pathways in SH-SY5Y cells. Our findings suggest that sulfuretin might be one of the potential candidates for the treatment of PD. View Full-Text
Keywords: sulfuretin; Parkinson’s disease; MPP+; apoptosis; Akt; GSK3β; ERK; p53 sulfuretin; Parkinson’s disease; MPP+; apoptosis; Akt; GSK3β; ERK; p53

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Pariyar, R.; Lamichhane, R.; Jung, H.J.; Kim, S.Y.; Seo, J. Sulfuretin Attenuates MPP+-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways. Int. J. Mol. Sci. 2017, 18, 2753.

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