Integrated bioinformatics analysis of the shared molecular mechanisms between Parkinson's disease and COVID-19.

To investigate the shared molecular mechanisms between Parkinson's disease (PD) and COVID-19 through integrated bioinformatics analysis and single-cell RNA sequencing (scRNA-seq). We conducted a comprehensive analysis of bulk RNA-seq data from publicly available databases, along with scRNA-seq data from brain tissues of COVID-19 patients. Differential expression analysis identified 725 differentially expressed genes (DEGs) in COVID-19 and 633 in PD samples. A total of 77 overlapping DEGs were identified, highlighting common pathways associated with neuroinflammation and dopaminergic neuron dysfunction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed significant enrichment in inflammation-related pathways. The protein-protein interaction network analysis identified CHI3L1 as a key gene linking PD and COVID-19. ScRNA-seq analysis revealed a significant increase in CHI3L1-expressing astrocytes in COVID-19 samples, indicating a potential mechanism by which COVID-19 may exacerbate PD symptoms. Furthermore, cell-cell communication analysis revealed enhanced interactions between astrocytes and microglia, excitatory neurons, or oligodendrocytes through signaling molecules such as phosphoprotein 1, CADM1, NCAM1, NRG, and NRXN1, suggesting that astrocytes play a central role in regulating neuronal excitability, synaptic plasticity, and immune responses in the context of COVID-19. These findings suggest a complex interplay between COVID-19 and PD, emphasizing the need for further investigation into the shared pathogenic mechanisms and potential therapeutic targets.IMPORTANCEThis study demonstrates the critical role of neuroinflammation and dopaminergic neuron damage in the shared pathogenesis of COVID-19 and Parkinson's disease. CHI3L1 emerges as a key target, highlighting its potential involvement in modulating neuroinflammatory pathways and synaptic plasticity. The functional significance of CHI3L1, along with its pathological relevance, warrants further investigation through larger studies. Additionally, the active intercellular communication among astrocytes, microglia, and excitatory neurons underscores the profound impact of COVID-19 on neural circuitry. Collectively, these results provide important insights into the mechanisms driving the neurodegenerative consequences of COVID-19, emphasizing the need for continued exploration of therapeutic interventions and the long-term neurological effects of viral infection.