AUTHOR=Filareti Melania , Luotti Silvia , Pasetto Laura , Pignataro Mauro , Paolella Katia , Messina Paolo , Pupillo Elisabetta , Filosto Massimiliano , Lunetta Christian , Mandrioli Jessica , Fuda Giuseppe , Calvo Andrea , Chiò Adriano , Corbo Massimo , Bendotti Caterina , Beghi Ettore , Bonetto Valentina TITLE=Decreased Levels of Foldase and Chaperone Proteins Are Associated with an Early-Onset Amyotrophic Lateral Sclerosis JOURNAL=Frontiers in Molecular Neuroscience VOLUME=10 YEAR=2017 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00099 DOI=10.3389/fnmol.2017.00099 ISSN=1662-5099 ABSTRACT=
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention. Toward this aim a differential proteomic analysis was performed in peripheral blood mononuclear cells (PBMC) from a group of 16 ALS patients with an age of onset ≤55 years and a group of 16 ALS patients with an age of onset ≥75 years, and matched healthy controls. We identified 43 differentially expressed proteins in the two groups of patients. Gene ontology analysis revealed that there was a significant enrichment in annotations associated with protein folding and response to stress. We next validated a selected number of proteins belonging to this functional group in 85 patients and 83 age- and sex-matched healthy controls using immunoassays. The results of the validation study confirmed that there was a decreased level of peptidyl-prolyl