Progressive dopamine neuron degeneration in the substantia nigra pars compacta is considered the most prominent pathological characteristic of Parkinson's disease (PD). Currently, there is no cure, but only the capability to relieve the symptoms of PD. The conserved dopamine neurotrophic factor (CDNF) protects and rescues dopamine neurons in vivo. However, the molecular function of CDNF in PD remains unclear. In present study, we investigated the role and intrinsic mechanism of CDNF in preventing and reversing rat pheochromocytoma (PC12) cells from apoptosis induced by 6-hydroxydopamine (6-OHDA). We demonstrate that 6-OHDA induces cell death in PC12 cells, but that CDNF attenuates this effect in a dose-dependent manner. Further study shows that upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity are observed in a dose-dependent manner upon pre-treatment or post-treatment with CDNF, suggesting a pathway of regulation of apoptosis by CDNF. These data demonstrate that CDNF prevents the apoptosis of PC12 cells induced by 6-OHDA by modulating Bcl-2/Bax and caspase-3 activati