Regulatory role of LncRNA FMR1-AS1 in the pathogenesis of alzheimer’s disease based on bioinformatics and in vitro experimental validation
Abstract Alzheimer’s disease (AD) is a major cause of dementia, characterized by $$\beta$$ -amyloid (A $$\beta$$ ) plaque accumulation and Tau protein hyperphosphorylation. Although long non-coding RNAs (lncRNAs) have been implicated in neurodegenerative diseases, their roles in AD remain unclear. T...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-15242-y |
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| Summary: | Abstract Alzheimer’s disease (AD) is a major cause of dementia, characterized by $$\beta$$ -amyloid (A $$\beta$$ ) plaque accumulation and Tau protein hyperphosphorylation. Although long non-coding RNAs (lncRNAs) have been implicated in neurodegenerative diseases, their roles in AD remain unclear. This study analyzed RNA sequencing data from the brain tissues of 17 AD patients and 19 healthy controls (GEO: GSE138260) to construct a gene co-expression network and identified eight lncRNAs strongly associated with AD. FMR1-AS1 was selected for functional validation. In an A $$\beta$$ 1–42-induced SH-SY5Y neuronal injury model, overexpression of FMR1-AS1 significantly increased cell viability ( $$p < 0.01$$ ), inhibited apoptosis ( $$p < 0.01$$ ), and reduced Tau hyperphosphorylation ( $$p < 0.001$$ ). FMR1-AS1 also alleviated oxidative stress by lowering reactive oxygen species (ROS) levels ( $$p < 0.01$$ ), enhanced superoxide dismutase (SOD) activity ( $$p < 0.05$$ ), and decreased malondialdehyde (MDA) content ( $$p < 0.01$$ ). Knockdown of FMR1-AS1 exacerbated neuronal damage. These results demonstrate that FMR1-AS1 exerts neuroprotective effects by regulating apoptosis, oxidative stress, and Tau pathology. The study highlights FMR1-AS1 as a potential therapeutic target for AD and may advance the understanding of lncRNA-mediated regulatory mechanisms in neurodegeneration. |
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| ISSN: | 2045-2322 |