Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease

Abstract

The diagnosis of Parkinson's disease (PD) is currently based on the clinical evaluation of extrapyramidal signs with a considerable error rate. The identification of specific markers might allow PD diagnosis before the onset of classical motor symptoms. By two-dimensional electrophoresis we identified proteome alterations in T-lymphocytes of 17 control subjects and 15 PD patients. The observed changes were used to build predictive models that were verified by the leave-one-out cross-validation. We further built two functions able to stage the subjects. We chose to verify by Western blotting the identity of spots corresponding to β-fibrinogen and transaldolase, two recurrent proteins in six out of 20 spots. β-Fibrinogen levels are lowered in PD patients, whereas a heavy transaldolase set of isoforms was more abundant. Eventually, we identified a list of seven proteins showing different levels in early-onset with respect to late-onset PD patients.

The Role of Innate and Adaptive Immunity in Parkinson's Disease

“…Identification of such patterns could also be a useful biomarker. T cell biomarkers have been investigated and some candidate proteins have been identified within these cells such as β-fibrinogen and transaldolase [108]. The pathogenic relevance of these changes is not yet understood.…”

Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis

“…were analyzed by modifying a procedure developed for the analysis of 2-DE image quantifications. 2,4,50,51 Protein amounts were imported together with UniProtKB/Swiss-Prot AC and descriptions for each of the 36 LC-MS/MS experiments (four technical replicates, three independent experiments, three experimental conditions each). This procedure allowed identifying 537 proteins.…”

Glucose promotes resistance in lymphocytes against oxidative stress-induced apoptosis through signaling and metabolic pathways. Implications for Parkinson’s disease

“…Recent data suggest that dysregulation of G metabolism might represent an early metabolic biomarker of sporadic PD (6). Because lymphocytes express GLU-1 and GLU-3 transporter proteins (49), display molecular death machinery (50), and G metabolism (25) similar to neurons (8,47,51), we consider that lymphocyte cells represent a remarkable non-neural cell model to understanding the signaling and metabolic regulation of apoptosis in response to stressful stimuli. Therefore, the metabolism-OS-cell death axis is a fundamental issue in the therapeutic design to prevent, delay, or ameliorate the treatment of individuals at risk of PD as encountered in Antioquia, Colombia (52).…”

“…Lymphocytes represent a dopaminergic system to analyze the phenomenon of OS in this neurological disorder (8,9). Specifically, we (10,11) and others (12)(13)(14)(15)(16) have used lymphocytes to understand the relationship between OS phenomena and PD.…”