Abstract
The Parkinson disease (PD) is the second most common neurodegenerative disorder
affecting the central nervous system and motor functions. The biological
complexity of PD is yet to reveal potential targets for intervention or to slow
the disease severity. Therefore, this study aimed to compare the fidelity of
blood to substantia nigra (SN) tissue gene expression from PD patients to
provide a systematic approach to predict role of the key genes of PD
pathobiology. Differentially expressed genes (DEGs) from multiple microarray
data sets of PD blood and SN tissue from GEO database are identified. Using the
theoretical network approach and variety of bioinformatic tools, we prioritized
the key genes from DEGs. A total of 540 and 1024 DEGs were identified in blood
and SN tissue samples, respectively. Functional pathways closely related to PD
such as ERK1 and ERK2 cascades, mitogen-activated protein kinase (MAPK)
signaling, Wnt, nuclear factor-κB (NF-κB), and PI3K-Akt signaling were observed
by enrichment analysis. Expression patterns of 13 DEGs were similar in both
blood and SN tissues. Comprehensive network topological analysis and gene
regulatory networks identified additional 10 DEGs functionally connected with
molecular mechanisms of PD through the mammalian target of rapamycin (mTOR),
autophagy, and AMP-activated protein kinase (AMPK) signaling pathways. Potential
drug molecules were identified by chemical-protein network and drug prediction
analysis. These potential candidates can be further validated in vitro/in vivo
to be used as biomarkers and/or novel drug targets for the PD pathology and/or
to arrest or delay the neurodegeneration over the years, respectively.