Nitroproteomics of Peripheral Blood Mononuclear Cells from Patients and a Rat Model of ALS

Abstract

Increased levels of 3-nitrotyrosine in the central nervous system have been found in patients and mouse models of familial ALS (fALS), suggesting a possible use of nitrated proteins as biomarkers. We analyzed peripheral blood mononuclear cells (PBMCs), easily accessible samples, from sporadic ALS (sALS) patients and a rat model of fALS (a) to establish whether an increased level of nitrated proteins was present in PBMCs, too, and (b) to identify possible candidate biomarkers. With a proteomic approach, we identified for the first time the major overnitrated proteins in PBMCs from patients and rats at different disease stages. In the rats, their increased levels already were measured at a presymptomatic stage. Among them, actin, ATP synthase, and vinculin overlap between sALS patients and the rat model. Interestingly, in a previous study, actin and ATPase have been found overnitrated in the spinal cord of a mouse model of fALS before disease onset, suggesting their possible involvement in motor neuron degeneration. In conclusion, we observed that an increased level of nitrated proteins was not restricted to the spinal cord but also was present in peripheral cells of patients and an animal model, and that nitrated proteins are promising candidate biomarkers for early diagnosis of ALS.