Integrated microarray analysis provided a new insight of the pathogenesis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease and the exact pathogenic mechanism remains mostly elusive. Our study aims to identify the key differentially expressed genes (DEGs) and up regulators in PD.

METHODS: An integrated analysis of microarray studies of PD was performed to identify the DEGs in PD compared to normal control (NC). Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions. Q-RT-PCR was performed to verify the expression of DEGs.

RESULTS: Seven datasets were obtained from GEO. A total of 276 DEGs (262 up-regulated and 14 down-regulated DEGs) in PD compared to normal control were identified with selecting criteria of p-value<0.05. GO terms of respiratory electron transport chain, protein binding and cytoplasm were significantly enriched in PD. Pathways of oxidative phosphorylation, Parkinson's disease, Alzheimer's disease and Huntington's disease were significantly enriched in PD. SNCA was the hub protein in PD according to the protein-protein interaction (PPI) network. The top 3 transcription factor (TFs) covering the most downstream DEGs were Oct-1, Pax-4 and Evi-1. A total of 19 DEGs were firstly identified in our integrated analysis, not from the other individual datasets enrolled in this study.

CONCLUSIONS: Several DEGs including SNCA, COX17, COX4I1, COX7B, COX6A1 and ATP5J targeted by Pax-4, Oct-1 and Evi-1 may involve in the neurodegeneration and pathogenesis of PD by regulating oxidative phosphorylation, ATP production and oxidative stress, which was benefit for uncovering the mechanism of PD and developing new diagnostic and therapeutic strategies.