Systems biology analysis of the proteomic alterations in Parkinson's disease: Common and disease-specific pathways

Objectives: Many biochemical mechanisms have been proposed to play a role in different neurodegenerative disorders. To distinguish what is disease-specific from what is generically linked to a neurodegenerative state is essential to better describe Parkinson's disease (PD) pathogenesis. PD and Amyotrophic Lateral Sclerosis (ALS) share some common mechanisms. Moreover, a high incidence of comorbidity may be explained by common biochemical altered pathways. Methods: We performed a bioinformatics meta-analysis of all the proteomic investigations of neuronal alterations in PD, ALS and Alzheimer's disease (AD), used as control (non-motor neurodegenerative disease). We combined these data with genes found in a curated disease-gene database (DisGeNET). Moreover, we are currently going to analyze Peripheral Blood Mononuclear Cells samples coming from 20 ALS patients, 20 PD patients and 20 comorbid ALS/PD patients by two-dimensional electrophoresis. Results: From our bioinformatics analysis some proteins were associated uniquely to PD, whereas others were associated to both diseases. Biological processes mostly associated to PD turned out to be chromatin organization, mitochondrion organization and protein folding. In addition, we found common dysregulated pathways, i.e., translation, SRP-dependent protein targeting to membrane and protein transport. Conclusions: PD and ALS pathogenesis have some common mechanisms, due to the fact that they are both neurodegenerative diseases. The combination of bioinformatics tools and proteomic analysis of samples coming from comorbid patients will allow u also to highlight the disease-specific pathways, which may justify the degeneration of different neuron populations.