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.

中文翻译：

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Peroxiredoxin 2 通过 N2a-APP 瑞典细胞中的 ROS–NRF2–p62 通路抑制 ROS 来改善 AβO 介导的自噬

在阿尔茨海默病中，活性氧 (ROS) 由淀粉样蛋白-β 寡聚体 (AβOs) 的沉积产生，这是神经元细胞死亡的重要原因之一。此外，已知 AβOs 通过 ROS 诱导诱导自噬。先前的研究表明，自噬上调会加重神经元细胞死亡。在这项研究中，研究了过氧化物酶 2 (Prx2)（抗氧化酶过氧化物酶家族的成员）对调节 AβO 介导的自噬的影响。Prx2 降低了 N2a-APPswe 细胞中 AβO 介导的氧化应激和自噬。此外，我们检查了 Prx2 的神经元保护作用与自噬减少之间的关系。与 N-乙酰半胱氨酸的作用相似，Prx2 通过下调 NRF2 的激活及其向细胞核的易位来降低 AβO 诱导的 ROS 并抑制 p62 蛋白表达水平。此外，用自噬抑制剂 3-甲基腺嘌呤治疗可改善神经元细胞死亡。总体而言，这些结果表明，Prx2 诱导的自噬减少与通过 N2a-APPswe 细胞中的 ROS-NRF2-p62 途径抑制 ROS 有关。因此，我们的研究结果表明，Prx2 是抗阿尔茨海默病治疗的潜在治疗靶点。