Nanogold induces anti-inflammation against oxidative stress induced in human neural stem cells exposed to amyloid-beta peptide. (May 2021)

• Record Type: Journal Article
• Authors: Chiang, Ming-Chang; Nicol, Christopher J.B.; Lin, Chien-Hung; Chen, Shiang-Jiuun; Yen, Chiahui; Huang, Rong-Nan
• Is Part Of: Neurochemistry international. Volume 145(2021)
• Publication Date: 2021-05
• Subjects: Alzheimer's disease -- Amyloid-beta -- Gold nanoparticles -- Human neural stem cells -- 3D bioprinter; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2021.104992
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss resulting in dementia. Amyloid-beta (Aβ) peptides play a critical role in the pathogenesis of the disease by promoting inflammation and oxidative stress, leading to neurodegeneration in the brains of AD patients. Numerous in vitro 3D cell culture models are useful mimics for understanding cellular changes that occur during AD under in vivo conditions. The 3D Bioprinter developed at the CELLINK INKREDIBLE was used in this study to directly investigate the influence of 3D conditions on human neural stem cells (hNSCs) exposed to Aβ. The development of anti-AD drugs is usually difficult, mainly due to a lack of therapeutic efficacy and enhanced serious side effects. Gold nanoparticles (AuNPs) demonstrate benefits in the treatment of several diseases, including AD, and may provide a novel therapeutic approach for AD patients. However, the neuroprotective mechanisms by which AuNPs exert these beneficial effects in hNSCs treated with Aβ are still not well understood. Therefore, we tested the hypothesis that AuNPs protect against Aβ-induced inflammation and oxidative stress in hNSCs under 3D conditions. Here, we showed that AuNPs improved the viability of hNSCs exposed to Aβ, which was correlated with the reduction in the expression of inflammatory cytokines, such as TNF-α and IL-1β. In addition, AuNPs rescued the levels of the transcripts of inhibitory kappa B kinase (IKK) in Aβ-treated hNSCs. The Aβ-mediated increases in mRNA, protein, and nuclear translocation levels of NF-κB (p65), a key transcription factor involved in inflammatory responses, were all significantly abrogated following co-treatment of hNSCs with AuNPs. In addition, treatment with AuNPs significantly restored iNOS and COX-2 levels in Aβ-treated hNSCs. Importantly, hNSCs co-treated with AuNPs were significantly protected from Aβ-induced oxidative stress, as detected using the DCFH-DA and DHE staining assays. Furthermore, hNSCs co-treated with 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, Gpx1, GSH, Catalase, and HO-1). Moreover, AuNPs reduced the aggregates and increased the proteasome activity and the expression of HSP27 and HSP70 genes in Aβ-treated hNSCs. Taken together, these findings provide the first evidence extending our understanding of the molecular mechanisms under 3D scaffold conditions by which AuNPs reverse the inflammation and oxidative stress-induced in hNSCs exposed to Aβ. These findings may facilitate the development of novel treatments for AD. Highlights: AuNPs rescues the Aβ-mediated decrease in cell viability and inflammation. AuNPs normalizes IKK and NF-κB expression in Aβ-exposed cells. AuNPs improves the Aβ-induced oxidative stress and downstream genes.