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Regulation of Survival Motor Neuron Protein by the Nuclear Factor-Kappa B Pathway in Mouse Spinal Cord Motoneurons
- Source :
- Recercat. Dipósit de la Recerca de Catalunya, instname, Repositorio Abierto de la UdL, Universitad de Lleida
- Publication Year :
- 2017
-
Abstract
- Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease. Using a lentiviral-based shRNA approach to reduce the expression of several members of NF-κB pathway, we observed that IKK and RelA knockdown caused Smn reduction in mouse-cultured motoneurons whereas IKK or RelB knockdown did not. Moreover, isolated motoneurons obtained from the severe SMA mouse model showed reduced protein levels of several NF-κB members and RelA phosphorylation. We describe the alteration of NF-κB pathway in SMA cells. In the context of recent studies suggesting regulation of altered intracellular pathways as a future pharmacological treatment of SMA, we propose the NF-κB pathway as a candidate in this new therapeutic approach. This work was supported by grants from Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias (PI14/00060), Unión Europea, Fondo europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa", and Generalitat de Catalunya (SGR740). AP holds a fellowship from Comissionat d’Universitats i Recerca, Departament d’Innovació, Universitats i Empresa de la Generalitat de Catalunya i Fons Social Europeu, SA and SdF hold a fellowship from Universitat de Lleida. We thank Elaine Lilly, Ph.D., for the English language revision of the manuscript.
- Subjects :
- 0301 basic medicine
Male
Neuroscience (miscellaneous)
RelA
Context (language use)
Mice, Transgenic
Biology
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
medicine
Animals
NF-kappaB
Phosphorylation
Cells, Cultured
Motor Neurons
Gene knockdown
musculoskeletal, neural, and ocular physiology
RELB
NF-kappa B
Spinal muscular atrophy
Motor neuron
medicine.disease
Spinal cord
SMA
Survival of Motor Neuron 1 Protein
SMN
Motoneurons
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
nervous system
Neurology
Gene Expression Regulation
Spinal Cord
Female
Neuroscience
Signal Transduction
Subjects
Details
- ISSN :
- 15591182
- Volume :
- 55
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology
- Accession number :
- edsair.doi.dedup.....cf0fad0da9482a31ba26709fd46351e1