Système moteur - Publications Scientifiques

Dernière publication 22/08/2019

Sp1-regulated expression of p11 contributes to motor neuron degeneration by memb

Disruption in membrane excitability contributes to malfunction and differential vulnerability of specific neuronal subpopulations in a number of...

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    [title] => Sp1-regulated expression of p11 contributes to motor neuron degeneration by memb
    [paragraph] => Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1
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Authors
V Garc’a-Morales, G Rodr’guez-Bey, L G—mez-PŽrez et al

 Lab
Grupo de Neurodegeneraci—n y Neurorreparaci—n (GRUNEDERE), Universidad de C‡diz, 11003 C‡diz, Spain
Journal
Nature Communications
Abstract
Disruption in membrane excitability contributes to malfunction and differential vulnerability of specific neuronal subpopulations in a number of neurological diseases. The adaptor protein p11, and background potassium channel TASK1, have overlapping distributions in the CNS. Here, we report that the transcription factor Sp1 controls p11 expression, which impacts on excitability by hampering functional expression of TASK1. In the SOD1-G93A mouse model of ALS, Sp1-p11-TASK1 dysregulation contributes to increased excitability and vulnerability of motor neurons. Interference with either Sp1 or p11 is neuroprotective, delaying neuron loss and prolonging lifespan in this model. Nitrosative stress, a potential factor in human neurodegeneration, stimulated Sp1 expression and human p11 promoter activity, at least in part, through a Sp1-binding site. Disruption of Sp1 or p11 also has neuroprotective effects in a traumatic model of motor neuron degeneration. Together our work suggests the Sp1-p11-TASK1 pathway is a potential target for treatment of degeneration of motor neurons.
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.
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