3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates MPP^＋-induced cytotoxicity by regulating oxidative stress and mitochondrial dysfunction in SH-SY5Y cells

Abstract

Parkinson’s disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against MPP+-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated MPP+-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of MPP+-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, Ca2+, and ATP in MPP+-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against MPP+-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin.

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

“…In this study, the SH-SY5Y cell line has been used as a model for PD since it has the machinery to synthesize DA (Krishna et al, 2014;Xicoy et al, 2017). MPP + is one of the most frequently used neurotoxins in creating cellular models and studying critical aspects of PD in SH-SY5Y cells (Yang et al, 2018;Chanthammachat and Dharmasaroja, 2019). Therefore, MPP + -induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms of PD.…”

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“…In this study, the SH-SY5Y cell line has been used as a model for PD since it has the machinery to synthesize DA (Krishna et al, 2014;Xicoy et al, 2017). MPP + is one of the most frequently used neurotoxins in creating cellular models and studying critical aspects of PD in SH-SY5Y cells (Yang et al, 2018;Chanthammachat and Dharmasaroja, 2019). Therefore, MPP + -induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms of PD.…”