Indirubin and Retinoic Acid Show Binding Affinity to Monocyte Biomarker CSF3R in Parkinson's Disease

This study integrated multi-omics data analysis to elucidate key molecular alterations associated with monocytes in Parkinson's disease (PD) so as to identify novel biomarkers.

Single-cell and chip datasets were derived from Gene Expression Omnibus (GEO) database. Single cell atlas of PD peripheral blood was delineated by Seurat package. CellChat was utilized for cell-cell communication analysis. Critical modules and Hub genes were screened by hdWGCNA. Differentially expressed genes (DEGs) between PD and control samples were recognized via Limma package, which were intersected with Hub genes to identify monocyte-related biomarkers. Functional enrichment analysis was conducted using GSEA_4.2.2 software. Targeted drugs of biomarkers were predicted to establish molecular docking models by AutoDocktools.

The single-cell data revealed that 10 cell subpopulations were identified in PD peripheral blood, of which CD8 ⁺ T cell and monocyte were relatively abundant and exhibited close intercellular communication. Thereafter, hdWGCNA screened two critical modules (Monocyte-M2, Monocyte-M5) and 20 Hub genes. Two monocyte-related biomarkers (CSF3R, IFITM3) were identified in PD peripheral blood, which were mainly involved in the immuno-inflammatory and neuronal-relevant pathways. Molecular docking models displayed that CSF3R could stably bind to Indirubin and Retinoic acid.

This study is the first to combine single-cell sequencing with hdWGCNA to identify two biomarkers closely associated with monocytes in peripheral blood from PD patients, while also predicting potential target drugs. These findings provide new evidence for elucidating the immunopathological mechanisms of PD and offer potential directions for future development of peripheral immune-based diagnostic strategies and targeted therapies.