https://scholars.lib.ntu.edu.tw/handle/123456789/572839
標題: | Nanogold induces anti-inflammation against oxidative stress induced in human neural stem cells exposed to amyloid-beta peptide | 作者: | Chiang M.-C Nicol C.J.B Lin C.-H Chen S.-J Yen C RONG-NAN HUANG SHIANG-JIUUN CHEN |
關鍵字: | 3D bioprinter; Alzheimer's disease; Amyloid-beta; Gold nanoparticles; Human neural stem cells | 公開日期: | 2021 | 卷: | 145 | 來源出版物: | Neurochemistry International | 摘要: | 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. ? 2021 Elsevier Ltd |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85101262977&doi=10.1016%2fj.neuint.2021.104992&partnerID=40&md5=26d7183b1607614d08ea2b2db12423b7 https://scholars.lib.ntu.edu.tw/handle/123456789/572839 |
ISSN: | 1970186 | DOI: | 10.1016/j.neuint.2021.104992 | SDG/關鍵字: | amyloid beta protein; catalase; copper zinc superoxide dismutase; cyclooxygenase 2; ethinylestradiol plus megestrol acetate; glutathione; glutathione peroxidase; glutathione peroxidase 1; gold nanoparticle; heat shock protein 27; heat shock protein 70; I |
顯示於: | 昆蟲學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。