BACKGROUND AND PURPOSE Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive memory loss in dementia. Gold nanoparticles (AuNPs) were reported beneficial for human neural stem cells (hNSCs) treated with Amyloid-beta (Aβ), but the neuroprotective mechanisms still are unknown. METHODS Cell Counting Kit-8 (CCK-8) was performed to detect hNSCs viability. The content of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) was analyzed by enzyme-linked immunosorbent (ELISA) assay. Immunocytochemistry was carried out to determinate Tuj-1 and glial fibrillary acidic protein (GFAP). The reactive oxygen species (ROS) and JC-1 assay kits were performed to detect ROS generation and mitochondrial membrane potential. Quantitative PCR (qPCR) and Western blot assessments were also used to detect related gene expression intracellularly or in the supernatant. RESULTS The pro-inflammation IL-6 and TNF-α were significantly decreased in the AuNPs co-treatment group. AuNPs could ameliorate neural stem cell differentiation inhibition due to Aβ accumulation. AuNPs co-treatment repressed the high expression of total tau (T-tau), phosphorylated tau (P-tau), and Aβ protein caused by the Aβ treatment. The apoptosis rate of hNSCs induced by Aβ was inhibited by AuNPs co-treatment and the expression of proteins associated with apoptosis was also reduced in AuNPs co-treatment group. Aβ-induced decreased mitochondrial membrane potential and mitochondria in the hNSCs were damaged, while AuNPs co-treatment showed the protective effect on mitochondrial membrane potential. Co-treatment with AuNPs significantly increased dynamin-related protein 1 (DRP1), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM) mRNA level. AuNPs may improve mitochondrial function impairment due to Aβ by elevating mitochondrial membrane potential, upregulating regulators of mitochondrial biogenesis, and inhibiting ROS production. hNSCs transfected with miR-21-5p inhibitor reversed AuNPs mediated cytoprotection induced by Aβ. miR-21-5p was involved in AuNPs protecting against Aβ-induced cell toxicity by reduced mitochondrial function. CONCLUSION AuNPs can protect hNSCs from Aβ injury by up-regulating miR-21-5p and protecting mitochondrial function.
Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive memory loss in dementia. Gold nanoparticles (AuNPs) were reported beneficial for human neural stem cells (hNSCs) treated with Amyloid-beta (Aβ), but the neuroprotective mechanisms still are unknown. Cell Counting Kit-8 (CCK-8) was performed to detect hNSCs viability. The content of interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α) was analyzed by enzyme-linked immunosorbent (ELISA) assay. Immunocytochemistry was carried out to determinate Tuj-1 and glial fibrillary acidic protein (GFAP). The reactive oxygen species (ROS) and JC-1 assay kits were performed to detect ROS generation and mitochondrial membrane potential. miRNA array was used to systematically detect the differential miRNAs. Dual-luciferase reporter assay was applied to verify the targeting relationship between miR-21-5p and the suppressor of cytokine signalling 6(SOCS6). Quantitative PCR (qPCR) and Western blot assessments were also used to detect related gene expression intracellularly or in the supernatant. The pro-inflammation IL-6 and TNF-α were significantly decreased in the AuNPs co-treatment group. AuNPs could ameliorate neural stem cell differentiation inhibition due to Aβ accumulation. AuNPs co-treatment repressed the high expression of total tau (T-tau), phosphorylated tau (P-tau), and Aβ protein caused by the Aβ treatment. The apoptosis rate of hNSCs induced by Aβ was inhibited by AuNPs co-treatment and the expression of proteins associated with apoptosis was also reduced in AuNPs co-treatment group. Aβ-induced decreased mitochondrial membrane potential and mitochondria in the hNSCs were damaged, while AuNPs co-treatment showed a protective effect on mitochondrial membrane potential. Co-treatment with AuNPs significantly increased dynamin-related protein 1 (DRP1), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM) mRNA levels. AuNPs may improve mitochondrial function impairment due to Aβ by elevating mitochondrial membrane potential, upregulating regulators of mitochondrial biogenesis, and inhibiting ROS production. hNSCs transfected with miR-21-5p inhibitor reversed AuNPs mediated cytoprotection induced by Aβ. miR-21-5p was involved in AuNPs protecting against Aβ-induced cell toxicity by reduced mitochondrial function. Overexpression of miR-21-5p contributes to enhancing the effect of cytoprotection of AuNPs. MiR-21-5p direct targeting SOCS6 and overexpression SOCS6 exerted opposite effects on hNSCs compared with miR-21-5p mimic. AuNPs can protect hNSCs from Aβ injury and decrease mitochondrial damage by regulating the miR-21-5p/SOCS6 pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.