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dc.contributor.authorArumugam, Saravanan
dc.contributor.authorTasheva, Stefka Mincheva
dc.contributor.authorPeriyakaruppiah, Ambika
dc.contributor.authorFuente Ruiz, Sandra de la
dc.contributor.authorSoler i Tatché, Rosa Ma.
dc.contributor.authorGarcera, Ana
dc.date.accessioned2018-04-06T07:49:01Z
dc.date.available2018-08-14T22:17:56Z
dc.date.issued2017-08-14
dc.identifier.issn0893-7648
dc.identifier.urihttp://hdl.handle.net/10459.1/63058
dc.description.abstractSurvival 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.
dc.description.sponsorshipThis 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.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherSpringer Verlag
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1007/s12035-017-0710-4
dc.relation.ispartofMolecular Neurobiology, 2018, vol. 55, núm. 6, p. 5019-5030
dc.rights(c) Springer Science+Business Media, LLC 2017
dc.subjectSMN
dc.subjectNF-kappaB
dc.subjectMotoneurons
dc.subjectSpinal muscular atrophy
dc.subjectRelA
dc.titleRegulation of survival motor neuron protein by the nuclear factor-kappa B pathway in mouse spinal cord motoneurons
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2018-04-06T07:49:02Z
dc.identifier.idgrec025924
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1007/s12035-017-0710-4


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