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
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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The lncRNA SOX21-AS1 is able to induce oxidative stress injury in neurons by up-regulating Wnt signaling in an AD mouse model.
“In addition, the lncRNA SOX21-AS1 is able to induce oxidative stress injury in neurons by up-regulating Wnt signaling in an AD mouse model [619].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [619]
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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
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- Authors
- Zhang, L., Fang, Y., Cheng, X., Lian, Y.-J., & Xu, H.-L.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Corresponding author
- Zhang, Lu
- Venue
- Molecular Neurobiology
- Published
- 2018-08-24
- Volume
- 56
- Issue
- 5
- Pages
- 3522-3537
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2888174210
- Cited by
- 88
- References
- 39
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 15 · 2020: 23 · 2019: 7 · 2018: 2
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, FZD3, FZD5, Wnt signaling, neuronal apoptosis, hippocampal neurons, β-catenin, cyclin D1, malondialdehyde, superoxide dismutase, glutathione peroxidase, learning and memory impairment, lncRNA silencing
- MeSH terms
- Alzheimer Disease, Animals, Base Sequence, Female, Hippocampus, Humans, Male, Memory, Neurons, RNA, Messenger, Up-Regulation, S Phase, Amyloid beta-Peptides, Apoptosis, Oxidative Stress, Gene Silencing, Frizzled Receptors, Mice, HEK293 Cells, Cell Cycle Checkpoints, Wnt Signaling Pathway, RNA, Long Noncoding
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