Research ReportMinocycline inhibits ICAD degradation and the NF-κB activation induced by 6-OHDA in PC12 cells

- Minocycline had a strong antioxidant effect to inhibit the cytotoxity.
- Minocycline also inhibited cell apoptosis in 6-OHDA induced PD model.
- Minocycline decreased p53 level and inhibited the nuclear translocation of NF-κB.

6-Hydroxydopamine (6-OHDA) is a neurotoxin that is commonly employed to induce lesions of the dopaminergic pathways to generating experimental models of Parkinson's disease (PD) in rodents. Antioxidant and anti-inflammatory therapy approaches have been the focus of attention in the treatment of neurodegenerative. PD and Alzheimer's diseases, and oxidative stress have been implicated in these diseases. In this study, we investigated the neuroprotective effects of minocycline and the signalling pathway that is possibly involved in a PC12 cell model of PD. The results indicated that 6-OHDA cytotoxicity was accompanied by an increment in lactate dehydrogenase (LDH) release, an increase in caspase-3 protein activity, an increase in ROS generation, MDA content and decrease in the SOD, CAT activities and cell viability. Moreover, treatment with 6-OHDA alone for 24 h resulted in ICAD degradation, increased nuclear translocation of NF-κB, and increased p53 expression. However, pretreatment with minocycline (5, 10, 20 µM) for 24 h significantly reduced LDH release, reduced caspase-3 protein production, reduced ROS production, MDA content and attenuated the decrease in SOD, CAT activities and cell viability. Additionally, minocycline (20 µM) markedly decreased the levels of cleaved ICAD protein, down-regulated p53 activity and inhibited the nuclear translocation of NF-κB. The neuroprotective effects of minocycline were attributable to its potent antioxidant activities, which prevented the nuclear translocation of NF-κB and the subsequent promotion of cell death. Therefore, the present study supports the notion that minocycline may be a promising neuroprotective agent for the treatment of Parkinson's disease.