Network Pharmacology of miR-146a-5p as a Potential Anti-Inflammatory Agent in Preventing Alzheimer's Disease

Alzheimer's disease is expressed as chronic neuroinflammation in the brain, which results in neuronal dysfunction, aberrant protein folding, and declining cognitive abilities. miR-146a-5p is a potent anti-inflammatory agent that can attenuate several inflammatory diseases and promote wound healing. Our research aimed to utilize network pharmacology to elucidate the therapeutic potential of miR-146a-5p in treating Alzheimer's disease using a biocomputational approach.

Alzheimer's disease genes were extracted from DisGeNET, OMIM, and GeneCards databases. At the same time, miR-146a-5p candidate genes were sourced from four prediction databases: miRDB, miRWalk, miRNet, and TargetScan.

The overlap between miR-146a-5p and Alzheimer's disease genes was established using STRING, with a score greater than 0.9, revealing a total of 157 nodes in the compound-target disease network.

Pathway enrichment analysis further revealed key candidate genes associated with Alzheimer's, including those involved in neuronal death, leukocyte migration, and axon development. EGFR, IL6, NFKB1, TLR4, CXCL8, FN1, CXCR4, and BCL2 were pinpointed as the top 8 key candidate genes of miR-146a-5p. Between these key candidate genes, the miR-146a-5p Regulatory Network also demonstrated that miR-146a-5p downregulates EGFR and CXCR4. Furthermore, this research revealed the regulatory network of miR-146a-5p, which modulates the transcriptional activities of IL6, NFKB1, TLR4, CXCL8, FN1, and BCL2.

Therefore, the current network pharmacology study explored the principal mechanism behind the anti-inflammatory effects of miR-146a-5p in treating Alzheimer's disease, and potentially to be applied to other neurodegenerative diseases.