期刊
MOLECULAR NEUROBIOLOGY
卷 55, 期 6, 页码 5019-5030出版社
SPRINGER
DOI: 10.1007/s12035-017-0710-4
关键词
SMN; NF-kappaB; Motoneurons; Spinal muscular atrophy; RelA
资金
- Ministerio de Economia y Competitividad
- Instituto de Salud Carlos III
- Fondo de Investigaciones Sanitarias [PI14/00060]
- Union Europea
- Fondo europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa
- Generalitat de Catalunya [SGR740]
- Comissionat d'Universitats i Recerca, Departament d'Innovacio, Universitats i Empresa de la Generalitat de Catalunya i Fons Social Europeu, SA
- Universitat de Lleida
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-kappa B pathway in regulating SMN in motoneurons. NF-kappa B is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-kappa B 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-kappa B 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-kappa B members and RelA phosphorylation. We describe the alteration of NF-kappa B 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-kappa B pathway as a candidate in this new therapeutic approach.
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