MicroRNA-gene regulatory network of TLR signaling in neuroinflammation-induced Parkinson’s disease: a bioinformatics approach

Parkinson’s disease (PD) is the second-most common neurodegenerative disease, affecting 10 million people worldwide. Neuroinflammation is one of the major pathologic processes in the development of PD. Neuroinflammation is promoted via the activation of TLRs present on immune cells in the brain. In addition, miRNA regulates TLR expression in neurodegenerative diseases. However, there is limited information on the miRNA that regulates TLR signaling genes in PD. In this study, we used GO, a bioinformatics tool that uses the representations for genes in an organism; PPI, which shows the physical interaction between proteins in an organism; and miRNet, a tool to navigate the complex relationships between miRNAs and their targets for deeper biologic understanding. To find out the potential TLR genes and regulatory miRNAs that play a role in neuroinflammation-induced PD. We acquired the gene expression profile, GSE26927, from the GEO Omnibus. DAVID bioinformatics and SHINY GO software were employed for GO analysis of DEGs, and the fold enrichment score for each pathway was verified. The TLR signaling pathways most deregulated genes (upregulated: log FC ≥ 2.0, downregulated: log FC ≤ – 2.0) were chosen for network analysis to identify crucial or hub genes. Subsequently, a miRNA-gene network was constructed using the miRNet tool. The foremost TLR signaling gene, distinguishing between PD and control samples, has been discerned. In the Protein–Protein Interaction (PPI) network, we identified genes with heightened connectivity, notably TLR4, exhibiting the highest degree of betweenness (degree = 22) in the TLR signaling pathway. Furthermore, in the miRNA-gene network, we unveiled the preeminent five miRNAs: hsa-miR-21-5p, hsa-miR-17-5p, hsa-miR-93-5p, hsa-miR-7-5p, and hsa-mir-92b-3p that interacted with the TLR signaling gene. The top ten TLR genes could be potential targets for new therapeutics. In addition, the identified potential miRNAs can strongly regulate the expression of TLR genes in PD and serve as therapeutic target.