title: Assessing the role of immuno-proteasomes in a mouse model of familial ALS.
abstract: The accumulation of protein aggregates is thought to be an important component in the pathogenesis of mutant SOD1-induced disease. Mutant SOD1 aggregates appear to be cleared by proteasomes, at least in vitro, suggesting a potentially important role for proteasome degradation pathways in vivo. G93A SOD1 transgenic mice show an increase in proteasome activity and induction of immuno-proteasome subunits within spinal cord as they develop neurological symptoms. To determine what role immuno-proteasomes may have in mutant SOD1-induced disease, we crossed G93A SOD1 transgenic mice with LMP2-/- mice to obtain G93A SOD1 mice lacking the LMP2 immuno-proteasome subunit. G93A SOD1/LMP2-/- mice show significant reductions in proteasome function within spinal cord compared to G93A SOD1 mice. However, G93A SOD1/LMP2-/- mice show no change in motor function decline, or survival compared to G93A SOD1 mice. These results indicate that the loss of immuno-proteasome function in vivo does not significantly alter mutant SOD1-induced disease.
authors.affiliation: Department of Neurology, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Puttaparthi
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Elliott
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000276:immunology* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D015854:Up-Regulation / Q000502:physiology
chemical_list: C000606290:SOD1 protein, human; C071313:LMP-2 protein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex