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Life Sci. 2019 Mar 15;221:259-266. doi: 10.1016/j.lfs.2019.02.025. Epub 2019 Feb 13.

Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway.

Author information

1
Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
2
Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
3
Department of Neurology, the First Hospital of Yu'lin, Yu'lin 718000, Shaanxi, China.
4
Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China. Electronic address: zhgl_2006@126.com.

Abstract

AIMS:

Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro.

MAIN METHODS:

Human neuroblastoma SH-SY5Y cells were pretreated with different concentrations of edaravone prior to the induction by Aβ25-35. Cell viability, apoptosis, reactive oxygen species, and expression of antioxidative response elements (ARE) including Nrf2, SOD, and HO-1 were assessed.

KEY FINDINGS:

The results showed that apoptosis and reactive oxygen species levels significantly increased in Aβ25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. The opposite changes were observed in cells that were pre-treated with edaravone, particularly at a concentration of 40 μM. Aβ25-35-treatment suppressed Nrf2 expression and nuclear translocation were rescued by Edaravone. Genetic inhibition of Nrf2 greatly decreased the protective effect of edaravone against cell apoptosis and cytotoxicity induced by Aβ25-35, accompanied by decreases in SOD and HO-1 expression.

SIGNIFICANCE:

Activation of the Nrf2/ARE signaling pathway may underlie the protective effects of edaravone against the oxidative damage associated with Alzheimer's disease.

KEYWORDS:

Alzheimer's disease; Aβ(25–35); Edaravone; Nrf2/ARE; Oxidative damage

PMID:
30769116
DOI:
10.1016/j.lfs.2019.02.025

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