title: Accumulation of misfolded SOD1 in dorsal root ganglion degenerating proprioceptive sensory neurons of transgenic mice with amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs). Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1) gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1(G93A) mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sábado
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Casanovas
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Olga
authors.identifier: 0000-0001-7741-3223
authors.initials: O
authors.lastname: Tarabal
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Hereu
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Lídia
authors.initials: L
authors.lastname: Piedrafita
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Calderó
authors.affiliation: Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina, IRBLLEIDA, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida, Avenida Rovira Roure 80, Lleida, 25198 Catalonia, Spain.
authors.forename: Josep E
authors.initials: JE
authors.lastname: Esquerda
mesh_terms: D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D005727:Ganglia, Spinal / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D017510:Protein Folding; D011984:Sensory Receptor Cells / Q000201:enzymology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C109415:SOD1 G93A protein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1