Comprehensive analysis of core genes and key pathways in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease that occurs mostly in middle-aged and older adults. Its main pathological feature is the progressive death of substantia nigra dopaminergic neurons. As the world's population ages, the number of PD patients is increasing. In this study, we explored the relationship between PD and the cell cycle. In this study, we collected two independent PD transcriptomic datasets, GSE54536 and GSE6613, from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to identify dysregulated pathways in PD samples. Gene expression was verified by qPCR in PD patients. Nineteen pathways were negatively enriched in both the GSE54536 and GSE6613 datasets. Seven of these 19 pathways were cell cycle-related pathways, including the M/G1 transition, S phase, G1/S transition, mitotic G1-G1/S phases, CDT1 association with the CDC6 ORC origin complex, cell cycle checkpoints and synthesis of DNA. Next, we found that eight genes (PSMA4, PSMB1, PSMC5, PSMD11, MCM4, RPA1, POLE, and PSME4) were mainly enriched in the GSE54536 and GSE6613 datasets. In GSE54536, PSMA4, PSMB1, PSMC5, and PSME4 could significantly predict the occurrence of PD, whereas, in GSE6613, RPA1 and PSME4 could significantly predict the occurrence of PD. Only PSME4 showed significant results in both datasets. Finally, we assessed blood samples from PD patients and controls. Compared with the control samples, the PD samples had lower mRNA levels of PSME4. In summary,these findings can significantly enhance our understanding of the causes and potential molecular mechanisms of PD; the cell cycle signaling pathways and PSME4 may be therapeutic targets for PD.