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

Amyloid-beta (A beta) 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 A beta, which was correlated with decreased caspase 3 and caspase 9. Importantly, hNSCs cotreated with GSH-AuNPs were significantly protected from A beta-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 A beta-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 A beta-treated hNSCs. GSH-AuNPs normalized ER calcium and mitochondrial cytochrome c homeostasis in A beta-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 (PGC1 alpha, NRF-1 and Tfam) in A beta-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 A beta.

Automated summary

This study demonstrates that glutathione conjugated gold nanoparticles (GSH-AuNPs) have the potential therapeutic value for Alzheimer's disease (AD) by protecting neural stem cells (hNSCs) from A beta-induced oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. GSH-AuNPs restore the expression of key genes and maintain cellular homeostasis in A beta-treated hNSCs.