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.

• Authors: Richard L Jayaraj, Kuppusamy Tamilselvam, Thamilarasan Manivasagam, Namasivayam Elangovan
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 51 Issue 3 Pg. 863-70 (Nov 2013) ISSN: 1559-1166 [Electronic] United States
• PMID: 23900721 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• CNB 001
• Neuroprotective Agents
• Pyrazoles
• Rotenone
• Curcumin

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cell Line, Tumor
• Curcumin (analogs & derivatives, pharmacology, therapeutic use)
• Humans
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress
• Parkinsonian Disorders (drug therapy)
• Pyrazoles (pharmacology, therapeutic use)
• Rotenone (toxicity)