CX3CR1-TLR4 Axis as a Shared Neuroimmune Target in COVID-19 and Epilepsy: Integrative Transcriptomics and Gabapentin...

Area of Science:

• Immunology
• Neuroscience
• Genomics

Background:

• Neuroinflammation is a key feature of both COVID-19 and epilepsy.
• The shared immunogenomic mechanisms underlying these conditions are not well understood.

Purpose of the Study:

• To identify common immune-inflammatory transcriptomic signatures between COVID-19 and epilepsy.
• To explore potential drug repositioning candidates for neuroinflammatory conditions.

Main Methods:

• Integrated single-cell RNA-seq (COVID-19 PBMCs) and bulk RNA-seq (epilepsy hippocampus) data.
• Identified common differentially expressed genes (DEGs) and performed pathway enrichment analysis (GO/KEGG).
• Constructed protein-protein interaction (PPI) networks and utilized drug repositioning databases (LINCS L1000).

Main Results:

• Identified 25 shared DEGs, with 22 upregulated genes involved in cytokine-cytokine receptor interaction and NF-κB signaling.
• A CX3CR1-TLR4-centered immune module was identified.
• Gabapentin was proposed as a repositioning candidate targeting CX3CR1, TLR4, and SELPLG, with diagnostic value confirmed (AUC > 0.90 in epilepsy).

Conclusions:

• A shared CX3CR1-TLR4-NF-κB inflammatory axis exists in COVID-19 and epilepsy.
• Gabapentin demonstrates potential as a dual-action immunomodulator for neuroinflammatory conditions.
• This study provides a mechanistic basis for repurposing Gabapentin beyond seizure control.