Bioinformatics Analysis of GPCR Gene Expression in CNS Lesions of MS Patients (PP-18)

Background: Multiple Sclerosis (MS) is a neuroinflammatory disorder characterized by immune-mediated demyelination and neurodegeneration within the central nervous system (CNS). Emerging evidence implicates G-protein coupled receptors (GPCRs) as critical modulators in MS pathogenesis, particularly through their roles in immune regulation and neural signaling. Among the GPCRs, CCR5 and CXCR2 are of special interest due to their involvement in immune cell migration and inflammation within the CNS. CCR5, primarily expressed on monocytes and CD8+ T cells in MS lesions, contributes to monocyte and macrophage infiltration, while CXCR2 facilitates the recruitment of neutrophils to inflammatory sites. Both receptors are considered potential biomarkers and therapeutic targets for modulating disease progression in MS.

Methods: In this research, a differential gene expression analysis was performed to identify dysregulation of GPCRs in CNS lesions of MS patients. Using publicly accessible RNA-seq datasets (GSE234700, GSE214334, GSE138614), a comprehensive RNA-seq analysis pipeline was applied, including stringent quality control, sequence alignment, and differential expression analysis. Functional enrichment analysis was conducted to interpret the results within the context of biological pathways associated with MS.
Results: The analysis identified several GPCR genes with significantly altered expression in MS lesions. Functional enrichment indicated these genes’ involvement in immune modulation, inflammatory responses, and neural signaling. Notably, CCR5 and CXCR2 were highlighted as critical receptors that may serve as novel therapeutic targets in MS.
Conclusion: This bioinformatics study underscores the potential involvement of specific GPCRs, particularly CCR5 and CXCR2, in MS pathogenesis. Their roles in immune regulation and inflammation suggest they could be valuable biomarkers or targets for new therapeutic strategies. Further experimental validation is essential to explore the mechanistic roles of these GPCRs in MS, potentially leading to the development of targeted therapies.