Abstract
Alzheimer’s disease (AD) represents a progressive neurodegenerative disorder characterized by distinctive neuropathological changes. Recently, long noncoding RNAs (lncRNAs) have become a key area of interest due to their potential in AD therapy. Hence, the aim of the current study was to investigate the effect of lncRNA SOX21-AS1 on neuronal oxidative stress injury in mice with AD via the Wnt signaling pathway by targeting FZD3/5. Microarray analysis was performed to screen AD-related differentially expressed genes (DEGs). Following verification of the target relationship between SOX21-AS1 and FZD3/5, the contents of OH−, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined, with the expressions of SOX21-AS1, FZD3/5, β-catenin, cyclin D1, and 4-HNE in hippocampal neuron cells subsequently detected. Cell cycle distribution and apoptosis were evaluated. Bioinformatics analysis revealed that SOX21-AS1 was upregulated in AD, while highlighting the co-expression of SOX21-AS1 and FZD3/5 genes and their involvement in the Wnt signaling pathway. AD mice exhibited diminished memory and learning ability, increased rates of MDA, OH−, SOX21-AS1, 4-HNE, and elevated levels of hippocampal neuron cell apoptosis, accompanied by decreased levels of SOD, CAT, GSH-Px, FZD3/5, β-catenin, and cyclin D1. Silencing of SOX21-AS1 resulted in decreased OH−, MDA contents, SOX21-AS1, and 4-HNE, and increased SOD, CAT, GSH-Px, FZD3/5, β-catenin, and cyclin D1, as well as reduced apoptosis of hippocampal neuron cells. Taken together, the key findings of the present study demonstrated that silencing of lncRNA SOX21-AS1 could act to alleviate neuronal oxidative stress and suppress neuronal apoptosis in AD mice through the upregulation of FZD3/5 and subsequent activation of the Wnt signaling pathway.
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Zhang, L., Fang, Y., Cheng, X. et al. Silencing of Long Noncoding RNA SOX21-AS1 Relieves Neuronal Oxidative Stress Injury in Mice with Alzheimer’s Disease by Upregulating FZD3/5 via the Wnt Signaling Pathway. Mol Neurobiol 56, 3522–3537 (2019). https://doi.org/10.1007/s12035-018-1299-y
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DOI: https://doi.org/10.1007/s12035-018-1299-y