In Alzheimer's disease, reactive oxygen species (ROS) are generated by the deposition of amyloid-beta oligomers (AβOs), which represent one of the important causes of neuronal cell death. Additionally, AβOs are known to induce autophagy via ROS induction. Previous studies have shown that autophagy upregulation aggravates neuronal cell death. In this study, the effects of peroxiredoxin 2 (Prx2), a member of the peroxidase family of antioxidant enzymes, on regulating AβO-mediated autophagy were investigated. Prx2 decreased AβO-mediated oxidative stress and autophagy in N2a-APPswe cells. Further, we examined the relationship between the neuronal protective effect of Prx2 and a decrease in autophagy. Similar to the effects of N-acetyl cysteine, Prx2 decreased AβO-induced ROS and inhibited p62 protein expression levels by downregulating the activation of NRF2 and its translocation to the nucleus. In addition, treatment with 3-methyladenine, an autophagy inhibitor, ameliorates neuronal cell death. Overall, these results demonstrate that the Prx2-induced decrease in autophagy was associated with the inhibition of ROS via the ROS-NRF2-p62 pathway in N2a-APPswe cells. Therefore, our results revealed that Prx2 is a potential therapeutic target in anti-Alzheimer therapy.
Keywords: Alzheimer’s disease; N2a-APPswe cells; ROS–NRF2–p62 pathway; autophagy; cell death; oxidative stress; peroxiredoxin 2.