title: Altered intracellular localization of SOD1 in leukocytes from patients with sporadic amyotrophic lateral sclerosis.
abstract: Several lines of evidence support the hypothesis of a toxic role played by wild type SOD1 (WT-SOD1) in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). In this study we investigated both distribution and expression profile of WT-SOD1 in leukocytes from 19 SALS patients and 17 healthy individuals. Immunofluorescence experiments by confocal microscopy showed that SOD1 accumulates in the nuclear compartment in a group of SALS subjects. These results were also confirmed by western blot carried out on soluble nuclear and cytoplasmic fractions, with increased nuclear SOD1 level (p<0.05). In addition, we observed the presence of cytoplasmic SOD1 aggregates in agreement with an increased amount of the protein recovered by the insoluble fraction. A further confirmation of the overall increased level of SOD1 has been obtained from single cells analysis using flow cytometry as cells from SALS patients showed an higher SOD1 protein content (p<0.05). These findings add further evidence to the hypothesis of an altered WT-SOD1 expression profile in peripheral blood mononuclear cells (PBMCs) from patients with ALS suggesting that WT-SOD1 species with different degrees of solubility could be involved in the pathogenesis of the disease.
authors.affiliation: Laboratory of Experimental Neurobiology, "C. Mondino" National Neurological Institute, Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leoni
authors.forename: Pamela
authors.initials: P
authors.lastname: Milani
authors.forename: Orietta
authors.initials: O
authors.lastname: Pansarasa
authors.forename: Giuliano
authors.initials: G
authors.lastname: Mazzini
authors.forename: Stefania
authors.initials: S
authors.lastname: Guareschi
authors.forename: Elena
authors.initials: E
authors.lastname: Alvisi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ghiroldi
authors.forename: Luca
authors.initials: L
authors.lastname: Diamanti
authors.forename: Stefano
authors.initials: S
authors.lastname: Bernuzzi
authors.forename: Mauro
authors.initials: M
authors.lastname: Ceroni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cova
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000201:enzymology; D003710:Demography; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D042541:Intracellular Space / Q000201:enzymology*; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D059010:Single-Cell Analysis; D012995:Solubility; D013347:Subcellular Fractions / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1