Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson's disease and vascular parkinsonism.

Abstract

Parkinson's disease (PD) and vascular parkinsonism (VP) are characterized by similar neurological syndromes but differ in pathogenesis, morphology, and therapeutic approaches. The molecular genetic mechanisms of these pathologies are multifactorial and involve multiple biological processes. To comprehensively analyze the pathophysiology of PD and VP, the methods of systems biology and gene network reconstruction are essential. In the current study, we performed metabolomic screening of amino acids and acylcarnitines in blood plasma of three groups of subjects: PD patients, VP patients and the control group. Comparative statistical analysis of the metabolic profiles identified significantly altered metabolites in the PD and the VP group. To identify potential mechanisms of amino acid and acylcarnitine metabolism disorders in PD and VP, regulatory gene networks were reconstructed using ANDSystem, a cognitive system. Regulatory pathways to the enzymes converting significant metabolites were found from PD-specific genetic markers, VP-specific genetic markers, and the group of genetic markers common to the two diseases. Comparative analysis of molecular genetic pathways in gene networks allowed us to identify both specific and non-specific molecular mechanisms associated with changes in the metabolomic profile in PD and VP. Regulatory pathways with potentially impaired function in these pathologies were discovered. The regulatory pathways to the enzymes ALDH2, BCAT1, AL1B1, and UD11 were found to be specific for PD, while the pathways regulating OCTC, FURIN, and S22A6 were specific for VP. The pathways regulating BCAT2, ODPB and P4HA1 were associated with genetic markers common to both diseases. The results obtained deepen the understanding of pathological processes in PD and VP and can be used for application of diagnostic systems based on the evaluation of the amino acids and acylcarnitines profile in blood plasma of patients with PD and VP.