Sclérose Latérale Amyotrophique (SLA), ou Maladie de Charcot - page 2 - Publications Scientifiques

Dernière publication 19/11/2019

Necroptosis is dispensable for motor neuron degeneration in a mouse model of ALS

Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is proposed to occur by necroptosis, an inflammatory form of regulated cell death....

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    [title] => Necroptosis is dispensable for motor neuron degeneration in a mouse model of ALS
    [paragraph] => Necroptosis is dispensable for motor neuron degeneration in a mouse model of ALS
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Authors
T Wang, ND Perera, MDF Chiam, B Cuic et al

 Lab
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, 3010, Australia
Journal
Cell Death and Differentiation
Abstract
Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is proposed to occur by necroptosis, an inflammatory form of regulated cell death. Prior studies implicated necroptosis in ALS based on accumulation of necroptotic markers in affected tissues of patients and mouse models, and amelioration of disease in mutant superoxide dismutase 1 (SOD1G93A) mice with inhibition of the upstream necroptotic mediators, receptor interacting protein kinase 1 (RIPK1), and RIPK3. To definitively address the pathogenic role of necroptosis in ALS, we genetically ablated the critical terminal executioner of necroptosis, mixed lineage kinase domain-like protein (MLKL), in SOD1G93A mice. Disease onset, progression, and survival were not affected in SOD1G93A mice lacking MLKL. Motor neuron degeneration and activation of neuroinflammatory cells, astrocytes, and microglia, were independent of MLKL expression in SOD1G93A mice. While RIPK1 accumulation occurred in spinal cords of SOD1G93A mice in late stage disease, RIPK3 and MLKL expression levels were not detected in central nervous system tissues from normal or SOD1G93A mice at any disease stage. These findings demonstrate that necroptosis does not play an important role in motor neuron death in ALS, which may limit the potential of therapeutic targeting of necroptosis in the treatment of neurological disorders.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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