Differentially expressed long-chain noncoding RNAs in human neuroblastoma cell line (SH-SY5Y): Alzheimer's disease cell model.

A number of complex human diseases including neurological diseases is characterized by dysregulation of long-chain noncoding RNA (lncRNA). The pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder is believed to involve alterations in lncRNAs. However, the specific lncRNAs modified in AD remain to be determined. The aim of this study was to identify lncRNAs associated with AD using human neuroblastoma cell line (SH-SY5Y) treated with beta-amyloid (Aß) as a model of this disease. The differential expressions of lncRNA were compared between beta-amyloid (Aß) SH-SY5Y cells and normal SH-SY5Y cells utilizing Illumina X10 gene sequencing. The differential expression profiles of amyloid (Aß)-treated SH-SY5Y cells were determined and verified by qRT-PCR method. The expression levels of lncRNA were expressed by calculating the abundance of FPKM (measure gene expression). The differential expression of log2 (multiple change) >1 or log2 (multiple change) < -1 had statistical significance (P< .05). The differential expression profiles of amyloid (Aß)-treated SH-SY5Y cells showed 40 lncRNA were up-regulated, while 60 lncRNA were down-regulated. GO and KEGG analysis demonstrated that differentially expressed genes were predominantly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, p53 signaling pathway, hepatitis B, cell cycle, post-translational protein modification, and regulation. In conclusion, approximately 100 dysregulated lncRNA transcripts were found in amyloid (Aß)-treated SH-SY5Y cells and these lncRNAs may play an important role in the occurrence and development of AD through altered signal pathways.

The protective underlying mechanisms of Schisandrin on SH-SY5Y cell model of Alzheimer's disease.

The extract of Schisandrin a traditional Chinese medicine was postulated to be effective in prevention and treatment of Alzheimer's disease (AD). The aim of this study was to examine the underlying protective actions of Schizandrin using a human neuroblastoma cell line (SH-SY5Y). In particular Schizandrin-mediated effects on expression of glycogen synthase kinase (GSK)-3ß, protein kinase B (Akt) and Tau protein, known to be altered in AD were determined. In preliminary assays, various concentrations of Schisandrin were incubated SH-SY5Y cells to establish effects on cell viability and potential toxicity in further experimentation. Amyloid-ß (Aß1-42) peptide 10 µmol/L was used to induce in vitro AD model in SH-SY5Y. Exposure to Aß1-42 significantly reduced cell viability. Treatment with Schisandrin to Aß1-42 exposed cells increased cell viability compared to amyloid peptide; however only the 10 µmol/L Schisandrin concentration was effective in restoring cell viability to control. Western blot analysis demonstrated that Aß1-42 produced a significant decrease in p-Akt protein expression levels accompanied by marked elevation in p-tau and p-GSK-3ß protein expression levels. Addition of 10 µmol/L Schisandrin to amyloid-treated SH-SY5Y cells was found to significantly increase protein expression levels of p-Akt associated with reduction in expression levels of p-tau and p-GSK-3ß protein. Treatment with 10 µmol/L Schisandrin of SH-SY5Y cells with the p-Akt inhibitor LY294002 demonstrated that the herbal-induced rise in p-Akt protein expression was diminished by this inhibitor indicating that signal transduction occurred in the observed cellular effects. Evidence indicates that Schisandrin inhibition of Aß1-42 -mediated cellular damage in AD neurons may involve activation of the PI3K/Akt signaling pathway where up-regulation of p-Akt activity consequently leads downstream to decreased activity of p-GSK-3ß phosphorylation accompanied by reduced tau protein. Consequently, restoration of neuronal cell viability was noted. Our findings suggest that the use of Schisandrin may be considered beneficial as a therapeutic agent in AD.