Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City, 242, Taiwan.
Departments of Pathology & Molecular Medicine and Biomedical & Molecular Sciences, Queen's University, Kingston, ON, K7L 3N6, Canada; Cancer Biology and Genetics Division, Cancer Research Institute, Queen's University, Kingston, ON, K7L 3N6, Canada.
Free Radic Biol Med. 2022 Jul;187:185-201. doi: 10.1016/j.freeradbiomed.2022.05.025. Epub 2022 Jun 1.
Amyloid-beta (Aβ) peptides have a role in the pathogenesis of Alzheimer's disease (AD) and are thought to promote oxidative stress, endoplasmic reticulum (ER) stress and mitochondrial deficiency, causing neuronal loss in the AD brain. The potential applications of glutathione conjugated gold nanoparticles (GSH-AuNPs) suggest they might have therapeutic value. Several studies have demonstrated that the effects of nanoparticles could provide protective roles in AD. Here, we showed that GSH-AuNPs mediate the viability of human neural stem cells (hNSCs) with Aβ, which was correlated with decreased caspase 3 and caspase 9. Importantly, hNSCs co-treated with GSH-AuNPs were significantly protected from Aβ-induced oxidative stress, as detected using the DCFH-DA, DHE, and MitoSOX staining assays. Furthermore, hNSCs co-treated with GSH-AuNPs were significantly protected from the Aβ-induced reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2 downstream antioxidant target genes (SOD-1, SOD-2, Gpx, Catalase, and HO-1). In addition, GSH-AuNPs rescued the expression levels of ER stress-associated genes (Bip, CHOP, and ASK1) in Aβ-treated hNSCs. GSH-AuNPs normalized ER calcium and mitochondrial cytochrome c homeostasis in Aβ-treated hNSCs. Furthermore, treatment with GSH-AuNPs restored the levels of ATP, D-loop, mitochondrial mass, basal respiration, ATP-linked reparation, maximal respiration capacity, COX activity, mitochondrial membrane potential, and mitochondrial genes (PGC1α, NRF-1 and Tfam) in Aβ-treated hNSCs. Taken together, these findings extend our understanding of the protective effects of GSH-AuNPs against oxidative stress, ER stress and mitochondrial dysfunction in hNSCs with Aβ.
淀粉样蛋白-β（Aβ）肽在阿尔茨海默病（AD）的发病机制中起作用，被认为可促进氧化应激、内质网（ER）应激和线粒体缺陷，导致 AD 大脑中的神经元丢失。谷胱甘肽修饰的金纳米粒子（GSH-AuNPs）的潜在应用表明它们可能具有治疗价值。多项研究表明，纳米粒子的作用可能在 AD 中提供保护作用。在这里，我们表明 GSH-AuNPs 介导 Aβ 对人神经干细胞（hNSCs）活力的影响，这与 caspase 3 和 caspase 9 的减少相关。重要的是，用 GSH-AuNPs 共处理的 hNSCs 从 Aβ 诱导的氧化应激中显著得到保护，这可通过 DCFH-DA、DHE 和 MitoSOX 染色测定来检测。此外，用 GSH-AuNPs 共处理的 hNSCs 从 Aβ 诱导的核因子红细胞 2 相关因子 2（Nrf2）和 Nrf2 下游抗氧化靶基因（SOD-1、SOD-2、Gpx、Catalase 和 HO-1）表达减少中得到显著保护。此外，GSH-AuNPs 挽救了 Aβ 处理的 hNSCs 中 ER 应激相关基因（Bip、CHOP 和 ASK1）的表达水平。GSH-AuNPs 使 Aβ 处理的 hNSCs 中的 ER 钙和线粒体细胞色素 c 稳态正常化。此外，用 GSH-AuNPs 处理恢复了 Aβ 处理的 hNSCs 中 ATP、D 环、线粒体质量、基础呼吸、ATP 连接修复、最大呼吸能力、COX 活性、线粒体膜电位和线粒体基因（PGC1α、NRF-1 和 Tfam）的水平。总之，这些发现扩展了我们对 GSH-AuNPs 对 Aβ 处理的 hNSCs 中氧化应激、ER 应激和线粒体功能障碍的保护作用的理解。
