2',3'-Dideoxycytidine Protects Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.

2',3'-Dideoxycytidine Protects Dopaminergic Neurons in a Mouse Model of Parkinson's Disease. Neurochem Res. 2017 Jun 19;: Authors: Niu J, Xiong J, Hu D, Zeng F, Nie S, Mao S, Wang T, Zhang Z, Zhang Z Abstract DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP(+)). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay. We found that MPP(+) induced neuronal death and the activation of caspase-3 in a dose-dependent manner. The expression of DNA pol-β increased after the neurons were exposed to MPP(+). DNA pol-β siRNA or DNA pol-β inhibitor DDC attenuated neuronal death induced by MPP(+). In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, MPTP treatment triggered behavioral deficits and nigrostriatal lesions. Pretreatment with DDC attenuated MPTP-induced behavioral deficits, dopaminergic neuronal death and striatal dopamine depletion in the MPTP mouse model. These results indicate that DNA pol-β inhibitors may present a novel promising therapeutic...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research