Network Analysis Performed on Transcriptomes of Parkinson's Disease Patients Reveals Dysfunction in Protein Translation.

ABSTRACT

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra region of the brain. The hallmark pathological feature of PD is the accumulation of misfolded proteins, leading to the formation of intracellular aggregates known as Lewy bodies. Recent data evidenced how disruptions in protein synthesis, folding, and degradation are events commonly observed in PD and may provide information on the molecular background behind its etiopathogenesis. In the present study, we used a publicly available transcriptomic microarray dataset of peripheral blood of PD patients and healthy controls (GSE6613) to investigate the potential dysregulation of elements involved in proteostasis-related processes at the transcriptomic level. Our bioinformatics analysis revealed 375 differentially expressed genes (DEGs), of which 281 were down-regulated and 94 were up-regulated. Network analysis performed on the observed DEGs highlighted a cluster of 36 elements mainly involved in the protein synthesis processes. Different enriched ontologies were related to translation initiation and regulation, ribosome structure, and ribosome components nuclear export. Overall, this data consistently points to a generalized impairment of the translational machinery and proteostasis. Dysregulation of these mechanics has been associated with PD pathogenesis. Understanding the precise regulation of such processes may shed light on the molecular mechanisms of PD and provide potential data for early diagnosis.