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Purpose This study was aimed to explore the molecular mechanism of Parkinson's disease (PD) development and discover underlying pathways and genes associated with PD.Methods The microarray data of GSE22491 containing 10 samples from PD patients and 8 samples from healthy controls (HC) were downloaded from the Gene Expression Omnibus (GEO) database.The differentially expressed genes (DEGs) were identified by paired t-test.Then the DEGs were performed cluster and principal component analyses followed by Gene Ontology (GO) and pathway enrichment analyses and protein-protein interaction (PPI) network construction.Results Total 176 up-regulated DEGs and 49 down-regulated DEGs were identified.Totally, 39 GO terms and 72 pathways were closely related to PD.Pathway of neuronal system was enriched by 10 DEGs such as synapsin Ⅰ (SYN1), glutamate receptor, ionotropic, N-methyl D-aspartate 1 (GRIN1) and GRIN2D.In the PPI networks, 18 hub genes were obtained, such as GRIN2D and discs, large (Drosophila) homolog-associated protein 3 (DLGAP3).Conclusion The pathway of neuronal system and its enriched DEGs may play important roles in PD progression.The DEGs such as SYN1, GRIN1,GRIN2D and DLGAP3 may be biomarkers for PD diagnosis and treatment.