GSH-AuNP anti-oxidative stress, ER stress and mitochondrial dysfunction in amyloid-beta peptide-treated human neural stem cells

Abstract

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.

Keywords: Amyloid-beta; ER stress; GSH-AuNPs; Human neural stem cells; Mitochondrial dysfunction; Oxidative stress.