Abstract:
: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.
journal_name
Biochimiejournal_title
Biochimieauthors
Eum WS,Shin MJ,Lee CH,Yeo HJ,Yeo EJ,Choi YJ,Kwon HJ,Kim DS,Kwon OS,Lee KW,Han KH,Park J,Kim DW,Choi SYdoi
10.1016/j.biochi.2018.10.010subject
Has Abstractpub_date
2019-01-01 00:00:00pages
158-168eissn
0300-9084issn
1638-6183pii
S0300-9084(18)30292-Xjournal_volume
156pub_type
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