Role of the PSMC1 gene in the pathological progression of Parkinson’s disease

Objective: To explore the association between Parkinson’s disease (PD) and the expression of ubiquitin-related proteins, and to elucidate its potential significance. Methods: Differential expression analyses were performed using the GSE20141 , GSE7621 , and GSE20164 datasets to identify and intersect differentially expressed genes (DEGs). Functional enrichment analyses were conducted to further explore the biological significance of these DEGs. C57BL/6J mice were randomly divided into either a PD model group or a control group. Behavioral performance on the balance beam test and the expression levels of PSMC1, α-syn, UCH-1, and Parkin in the substantia nigra were compared between groups. Results: Gene overlap analysis across the three datasets identified 25 core DEGs, among which PSMC1 was the only ubiquitin-proteasome system (UPS)-related gene. Compared with the controls, the number of paw slips from balance beam in the model group significantly increased after 3, 6, and 10 modeling sessions (P<0.05). The mRNA expression levels of PSMC1, UCH-1, and Parkin in the substantia nigra of the model group mice significantly decreased (P<0.05), whereas the mRNA expression of α-syn significantly increased (P<0.05). Conclusions: Integrating bioinformatics with experimental verification, this study confirms that dysregulation of key UPS genes-particularly PSMC1-is closely related to the pathological process of PD.