Investigating the therapeutic mechanisms of dental pulp stem cells in Parkinson's disease: A bioinformatics-based multi-omics analysis

Biochem Biophys Res Commun. 2026 Jan 8:795:153127. doi: 10.1016/j.bbrc.2025.153127. Epub 2025 Dec 12.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. Dental pulp stem cells (DPSCs) have emerged as a promising therapeutic candidate due to their neurotrophic properties and potential to support neural regeneration. This study aimed to elucidate the molecular mechanisms linking DPSCs and PD using bioinformatics. To investigate the biological functions and signaling pathways related to differentially expressed genes (DEGs), we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and Gene Set Variation Analysis (GSVA). From 476 overlapping DEGs, three key genes, MGAT1, ARRB2, and COL15A1, were identified and validated using quantitative real-time PCR (qPCR) in a 6-OHDA-induced rat model of PD. All three genes showed significant dysregulation consistent with PD-related molecular changes. Molecular docking further demonstrated strong predicted binding affinities for MGAT1 with SRC kinase inhibitor II (-8.58 kcal/mol), ARRB2 with bezafibrate (-5.19 kcal/mol), and COL15A1 with ruxolitinib (-6.32 kcal/mol). In vivo qPCR analysis in the PD rat model confirmed downregulation of ARRB2 and MGAT1 and upregulation of COL15A1 (p < 0.05), supporting the bioinformatics findings. Overall, this multi-level analysis highlights potential mechanisms between DPSCs and PD, and identifies candidate genes and drug targets that may inform future therapeutic strategies.

Keywords: Bioinformatics analysis; Dental pulp stem cells; Molecular docking; Parkinson's disease; Protein-protein interaction network.

MeSH terms

  • Animals
  • Computational Biology* / methods
  • Dental Pulp* / cytology
  • Gene Expression Profiling
  • Humans
  • Male
  • Molecular Docking Simulation
  • Multiomics
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*
  • Stem Cells* / cytology
  • Stem Cells* / metabolism