Jin Wei, Kam Min Kyoung, Lee Sung Woo, Park Young-Ho, Lee Hong Jun, Lee Dong-Seok
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea.
School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 41566, Korea.
Antioxidants (Basel). 2022 Sep 23;11(10):1889. doi: 10.3390/antiox11101889.
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.
在阿尔茨海默病中，活性氧（ROS）由β淀粉样寡聚体（AβOs）沉积产生，而AβOs是神经元细胞死亡的重要原因之一。此外，已知AβOs通过诱导ROS来诱导自噬。先前的研究表明，自噬上调会加重神经元细胞死亡。在本研究中，对过氧化物酶家族抗氧化酶成员之一的过氧化物酶2（Prx2）在调节AβO介导的自噬方面的作用进行了研究。Prx2可降低N2a-APPswe细胞中AβO介导的氧化应激和自噬。此外，我们研究了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类似，Prx2可降低AβO诱导的ROS，并通过下调NRF2的激活及其向细胞核的转位来抑制p62蛋白表达水平。此外，用自噬抑制剂3-甲基腺嘌呤处理可改善神经元细胞死亡。总体而言，这些结果表明，在N2a-APPswe细胞中，Prx2诱导的自噬减少与通过ROS-NRF2-p62途径抑制ROS有关。因此，我们的结果表明Prx2是抗阿尔茨海默病治疗中的一个潜在治疗靶点。
