Neuroprotective effects of antioxidants, Idebenone and Ferulic Acid, in MPP(+)-induced PC12 cells, as a model of Parkinson's disease.

摘要

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by intraneuronal proteinaceous cytoplasmic inclusions known as Lewy bodies, mainly composed of α-synuclein. α-synuclein protein is reported to be associated with mitochondrial dysfunction and oxidative stress leading to the activation of proinflammatory factors and mitochondria-dependent apoptotic pathways, and subsequent neuronal death. Idebenone, a Coenzyme Q10 analogue, having anti-oxidant properties, may prove neuroprotective by acting directly as electron acceptor for the mitochondrial electron transport chain (ETC) complexes. Ferulic Acid, a polyphenol, postulated to have a strong anti-oxidant potential, may also have neuroprotective effects.;Objective: The present study investigated the protective effects of Idebenone and Ferulic acid against MPP+-induced oxidative stress and neurodegeneration in PC12 cells and compared their effects on α-synuclein expression and the potential modulation of NF-κB, COX-2 expression, as well as ROS production and anti-apoptotic effects.;Methods: PC12 cells were pretreated with different concentrations of Idebenone and Ferulic Acid prior to exposure to MPP+, and cell viability was assessed by MTT Assay. Effect of the drugs on the expression of α-synuclein, NF-κB, COX-2, Bax and Bcl-2 was assessed by western blot analysis, whereas, the effect on ROS production was investigated by DCF assay.;Results: Results demonstrated that pretreatment with Idebenone and Ferulic Acid not only protected the PC12 cells from MPP+-induced toxicity by increasing cell viability, but also by significantly suppressing the MPP+-induced increases in -synuclein, COX-2 and NF-κB expression in a dose-dependent manner. In addition, the ROS levels, and Bax/Bcl-2 ratio for Idebenone and Ferulic acid were significantly decreased as compared to the increased levels seen with the toxin.;Conclusion: This study emphasizes the significant link between mitochondrial distress, protein aggregation, oxidative stress, and apoptosis in relation to Parkinson's disease and also suggests that the neuroprotection offered by the two drugs may be anti-oxidative as well as anti-apoptotic in nature.