Neuroprotective effects of Tat-ATOX1 protein against MPP⁺-induced SH-SY5Y cell deaths and in MPTP-induced mouse model of Parkinson's disease

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>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<SUP>+</SUP>)-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<SUP>+</SUP> 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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Tat-ATOX1 transduces into SH-SY5Y cells and inhibited MPP<SUP>+</SUP>-induced cell death. </LI> <LI> Tat-ATOX1 suppressed the activation of Akt and MAPKs in MPP<SUP>+</SUP> exposed SH-SY5Y cells. </LI> <LI> Tat-ATOX1 inhibited dopaminergic neuronal cell loss in MPTP-induced animal model. </LI> <LI> Tat-ATOX1 represent a potential therapeutic agent for PD. </LI> </UL> </P>