GPX3 as a Novel and Potential Therapeutic Target in the Shared Molecular Mechanisms of Traumatic Brain and Parkinson's Disease

Background: Traumatic brain injury (TBI) is a prevalent neurological disorder associated with significant public health burdens and long-term risks, including neurodegenerative diseases such as Parkinson's disease (PD). Emerging evidence suggests a strong link between moderate to severe TBI and an elevated risk of PD, though the underlying mechanisms remain poorly understood. Materials and Methods: Common differentially expressed genes (DEGs) were identified in GEO datasets of patients with traumatic brain injury (TBI) and Parkinson's disease (PD). Further analyses, including GO and KEGG pathway enrichment, protein-protein interaction (PPI) network construction, hub gene identification, as well as miRNA and transcription factor prediction and drug candidate screening, were conducted. Subsequently, the expression of hub genes was validated using additional TBI- and PD-related GEO datasets and the Comparative Toxicogenomics Database (CTD). Finally, the expression of hub genes was further validated in a mouse model of TBI induced by controlled cortical impact (CCI). Results: Shared transcriptional signatures between TBI and PD were uncovered, highlighting overlapping molecular networks and pathways. The glutathione peroxidase 3 (GPX3) gene emerged as a pivotal hub gene, with its expression significantly altered in both TBI and PD datasets. Conclusion: This study underscores the critical role of GPX3 in the molecular intersection of TBI and PD, suggesting it as a novel and potential therapeutic target, offering new insights into potential therapeutic strategies.