Back to Search
Start Over
2′,3′-Dideoxycytidine Protects Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.
- Source :
- Neurochemical Research; Oct2017, Vol. 42 Issue 10, p2996-3004, 9p
- Publication Year :
- 2017
-
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 option for the neuroprotective treatment of PD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03643190
- Volume :
- 42
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Neurochemical Research
- Publication Type :
- Academic Journal
- Accession number :
- 125460669
- Full Text :
- https://doi.org/10.1007/s11064-017-2330-9