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Parkinson disease (PD) is well known that a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays critical roles in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, linked to autosomal recessive early onset of PD by loss-of-function. Therefore, we investigated the protective effects of transduced Tat-DJ-1 protein against SH-SY5Y cells and PD mouse model. Tat-DJ-1 protein rapidly transduced into the cells and shows protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reduced the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in the 1-methyl-4-phenyl-1, 2, 3, 6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential strategy for therapeutic delivery in various human diseases including PD.