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صفحه اصلی
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4th international edition and 13th Iranian Conference on Bioinformatics
Exploring the Regulatory Landscape of LncRNAs in Alzheimer’s Disease: Insights into Inflammation
نویسندگان :
Narjes Khatoun Shabani Sadr
1
Farideh Faramarzi
2
Mehrdad Behmanesh
3
1- tarbiat modares university
2- tarbiat modares university
3- tarbiat modares university
کلمات کلیدی :
Alzheimer’s disease (AD)،LncRNA،Neuroinflammation،RNA-Seq،Biomarkers
چکیده :
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline, synaptic dysfunction, and widespread gene expression changes (Zhang et al., 2024a). Among regulatory elements, long non-coding RNAs (LncRNAs) have emerged as pivotal modulators of biological processes, influencing pathways associated with inflammation (Statello et al., 2021; Zhang et al., 2024b; Lan et al., 2022). This study applies a bioinformatics approach to explore the regulatory role of LncRNAs in AD pathogenesis, with a focus on their contributions to neuroinflammation. RNA-Seq datasets from multiple brain regions, including hippocampus, frontal lobe, parietal lobe, occipital lobe and temporal lobe, were obtained from public repository, Gene Expression Omnibus (GEO) database. After preprocessing, differential expression analysis (DEG) identified key LncRNAs with significant dysregulation in AD patients compared to controls (Koch et al., 2018; Corchete et al., 2020). Functional enrichment analysis was performed using tools such as Enrichr and GSEA to map these LncRNAs to specific biological pathways. Furthermore, gene regulatory networks were constructed to identify interactions between LncRNAs and genes involved in inflammatory. The analysis revealed multiple differentially expressed LncRNAs with significant roles in modulating key pathways. For instance, LncRNAs associated with the NF-κB pathway were found to amplify neuroinflammatory responses by upregulating cytokines like TNFα and IL-6. Expression patterns of these LncRNAs were strongly correlated with disease severity, indicating their potential as biomarkers (Garofalo et al., 2021) for disease progression. In addition to their impact on protein-coding genes, several LncRNAs were identified as regulators of microglial and astrocytic activity, linking cellular neuroinflammation to systemic metabolic dysregulation. This integrative approach underscores the complex interplay between LncRNAs and AD-related pathways. Conclusion: This study highlights the multifaceted regulatory role of LncRNAs in Alzheimer’s disease, offering novel insights into their contributions to inflammation. The findings suggest that targeting specific LncRNAs could provide therapeutic opportunities to mitigate AD progression. Future work will focus on experimental validation and exploring the translational potential of these findings.
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