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dc.contributor.authorSábado, Javier
dc.contributor.authorCasanovas i Llorens, Anna
dc.contributor.authorTarabal Mostazo, Olga
dc.contributor.authorHereu, Marta
dc.contributor.authorPiedrafita Llorens, Lídia
dc.contributor.authorCalderó i Pardo, Jordi
dc.contributor.authorEsquerda Colell, Josep
dc.identifier.issn2314-6141 (versió electrònica)
dc.description.abstractAmyotrophic 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.
dc.description.sponsorshipThe authors would like to thank Montse Ortega for her technical assistance and Claudia Cervero, Alexandra Eritja and Ariadna Salvador for their help with some of the experiments in this study. This work was supported by grants from the Ministerio de Ciencia y Tecnologia and Ministerio de Economia y Competitividad and cofinanced by FEDER (SAF2011-22908; SAF2012-31831).
dc.publisherHindawi Publishing Corporation
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofBioMed Research International, 2014, vol. 2014, num. 852163, p. 1-13
dc.rightscc-by, (c) Sábado et al., 2014
dc.subjectEsclerosis lateral amiotrófica
dc.subjectNeuronas motoras
dc.subjectMouse model
dc.subjectFals mice
dc.subject.classificationEsclerosi lateral amiotròfica
dc.subject.classificationNeurones motores
dc.subject.otherAmyotrophic lateral sclerosis
dc.subject.otherMotor neurons
dc.titleAccumulation of misfolded SOD1 in dorsal root ganglion degenerating propioceptive sensory neurons of transgenic mice with amyotrophic lateral sclerosis

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cc-by, (c) Sábado et al., 2014
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