Accumulation of misfolded SOD1 in dorsal root ganglion degenerating propioceptive sensory neurons of transgenic mice with amyotrophic lateral sclerosis
Data de publicació2014
Casanovas i Llorens, Anna
MetadadesMostra el registre d'unitat complet
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.
És part deBioMed Research International, 2014, vol. 2014, num. 852163, p. 1-13
Projectes de recerca europeus
Mostrant elements relacionats per títol, autor i matèria.
Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury Casanovas i Llorens, Anna; Salvany, Sara; Lahoz, Víctor; Tarabal Mostazo, Olga; Piedrafita Llorens, Lídia; Sabater, Raimundo; Hernández, Sara; Calderó i Pardo, Jordi; Esquerda Colell, Josep (Nature, 2017)The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display ...
Microglial recruitment and mechanisms involved in the disruption of afferent synaptic terminals on spinal cord motor neurons after acute peripheral nerve injury Salvany, Sara; Casanovas i Llorens, Anna; Piedrafita Llorens, Lídia; Tarabal Mostazo, Olga; Hernández, Sara; Calderó i Pardo, Jordi; Esquerda Colell, Josep (Wiley, 2021-01-02)Peripheral nerve section with subsequent disconnection of motor neuron (MN) cell bodies from their skeletal muscle targets leads to a rapid reactive response involving the recruitment and activation of microglia. In addition, ...
Glial activation and central synapse loss, but not motoneuron degeneration, are prevented by the sigma-1 receptor agonist PRE-084 in the Smn2B/- mouse model of spinal muscular atrophy Cerveró Cebrià, Clàudia; Blasco Carmona, Alba; Tarabal Mostazo, Olga; Casanovas i Llorens, Anna; Piedrafita Llorens, Lídia; Navarro, X. (Xavier); Esquerda Colell, Josep; Calderó i Pardo, Jordi (American Association of Neuropathologists, 2018)Spinal muscular atrophy (SMA) is characterized by the loss of α-motoneurons (MNs) with concomitant muscle denervation. MN excitability and vulnerability to disease are particularly regulated by cholinergic synaptic afferents ...