Parkinson's disease (PD), a neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra (SN) of the brain and it is well known that the pathogenesis of PD is related to a number of risk factors including oxidative stress. Antioxidant 1 (ATOX1) protein plays a crucial role in various diseases as an antioxidant and chaperone. In this study, we determined whether Tat-ATOX1 could protect against 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced SH-SY5Y cell death and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD. In the MPP⁺ exposed SH-SY5Y cells, Tat-ATOX1 markedly inhibited cell death and toxicities. In addition, Tat-ATOX1 markedly suppressed the activation of Akt and mitogen activated protein kinases (MAPKs) as well as cleavage of caspase-3 and Bax expression levels. In a MPTP-induced animal model, Tat-ATOX1 transduced into brain and protected dopaminergic neuronal cell loss. Taken together, Tat-ATOX1 inhibits dopaminergic neuronal death through the suppression of MAPKs and apoptotic signal pathways. Thus, Tat-ATOX1 represents a potential therapeutic protein drug candidate for PD.

帕金森氏病（PD）是一种神经退行性疾病，其特征是大脑黑质（SN）中的多巴胺能神经元缺失，众所周知，PD的发病机理与包括氧化应激在内的许多危险因素有关。抗氧化剂1（ATOX1）蛋白作为抗氧化剂和伴侣蛋白在各种疾病中起着至关重要的作用。在这项研究中，我们确定Tat-ATOX1是否可以防御1-甲基-4-苯基吡啶鎓离子（MPP ⁺）诱导的SH-SY5Y细胞死亡以及1-甲基-4-苯基-1,2,3,6 -四氢吡啶（MPTP）诱导的PD动物模型。在MPP ⁺暴露于SH-SY5Y细胞后，Tat-ATOX1明显抑制细胞死亡和毒性。此外，Tat-ATOX1显着抑制Akt和有丝分裂原激活的蛋白激酶（MAPK）的激活以及caspase-3和Bax表达水平的切割。在MPTP诱导的动物模型中，Tat-ATOX1转导进入大脑并保护了多巴胺能神经元细胞的丢失。总之，Tat-ATOX1通过抑制MAPK和凋亡信号通路来抑制多巴胺能神经元死亡。因此，Tat-ATOX1代表PD的潜在治疗性蛋白质药物候选者。