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Neuroprotective Effect of CNB-001, a Novel Pyrazole Derivative of Curcumin on Biochemical and Apoptotic Markers Against Rotenone-Induced SK-N-SH Cellular Model of Parkinson’s Disease

Abstract

Oxidative stress and mitochondrial dysfunction are underpinned for initiating a cascade of toxic events leading to dopaminergic neuronal death in Parkinson’s disease (PD) and identified as vital target for therapeutic intervention. Curcumin, a potent antioxidant has been reported to display diverse neuroprotective properties against various neurodegenerative diseases including PD. In this present study, we investigated the protective effect of CNB-001, a pyrazole derivative of curcumin on rotenone-induced toxicity and its possible mechanisms in neuroblastoma SK-N-SH cells. Rotenone insult significantly reduced cell viability (MTT assay) and resulted in 78 % apoptosis (dual staining) by altering Bcl-2, Bax, caspase-3, and cytochrome C expression. Moreover, rotenone enhanced ROS production and disrupts mitochondrial membrane potential. These resultant phenotypes were distinctly alleviated by CNB-001. Pretreatment with CNB-001(2 μM) 2 h before rotenone exposure (100 nM) increased cell viability, decreased ROS formation, maintained normal physiological mitochondrial membrane potential, and reduced apoptosis. Furthermore, CNB-001 inhibited downstream apoptotic cascade by increasing the expression of vital antiapoptotic protein Bcl-2 and decreased the expression of Bax, caspase-3, and cytochrome C. Collectively, the results suggest that CNB-001 protects neuronal cell against toxicity through antioxidant and antiapoptotic properties through its action on mitochondria. Therefore, it may be concluded that CNB-001 can be further developed as a promising drug for treatment of PD.

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Acknowledgment

We are very much thankful to Dr. Dave Schubert (Cellular Neurobiology lab) at Salk Institute of Biological sciences for his constant advice and generosity in providing CNB-001.

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Correspondence to Namasivayam Elangovan.

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Jayaraj, R.L., Tamilselvam, K., Manivasagam, T. et al. Neuroprotective Effect of CNB-001, a Novel Pyrazole Derivative of Curcumin on Biochemical and Apoptotic Markers Against Rotenone-Induced SK-N-SH Cellular Model of Parkinson’s Disease. J Mol Neurosci 51, 863–870 (2013). https://doi.org/10.1007/s12031-013-0075-8

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Keywords

  • CNB-001
  • Rotenone
  • Oxidative stress
  • Mitochondria membrane potential
  • Apoptosis