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dc.contributor.authorPeriyakaruppiah, Ambika
dc.contributor.authorFuente Ruiz, Sandra de la
dc.contributor.authorArumugam, Saravanan
dc.contributor.authorBahi i Pla, Núria
dc.contributor.authorGarcera, Ana
dc.contributor.authorSoler i Tatché, Rosa Ma.
dc.date.accessioned2017-01-18T13:37:27Z
dc.date.issued2016
dc.identifier.issn0014-4886
dc.identifier.urihttp://hdl.handle.net/10459.1/59027
dc.description.abstractSpinalMuscular Atrophy (SMA), a neurodegenerative disorder primarily affecting motoneurons (MNs), is caused by the loss of the Survival Motor Neuron 1 (SMN1) gene and reduced levels of full-length survival motor neuron (SMN) protein. The exact cellular/molecular mechanisms involved in SMN-induced MN degeneration are under study. Autophagy is a degradation pathway whose precise roles in neurodegeneration remain largely unknown, but abnormal autophagy has a central role in some neurodegenerative diseases, including MN disorders. The analysis of the autophagy response in SMA and its role in the development of the disease could be essential to understand the disease. In the present work, we describe an increase of autophagosomes and LC3-II protein in spinal cord MNs of severe SMA mouse model. A time-course experiment demonstrated increased LC3-II levels fromembryonic to postnatal stage, suggesting a deregulation of the autophagy process as the disease progressed. Using an in vitro model ofMN culture, we analyzed the effect of autophagy modulators on Smn (murine survival motor neuron) protein level. Results suggest that the inhibitors of the autophagy flux cause reduction ofSmn protein, whereas autophagy inducers increase the level of Smn protein inMNs. In order to evaluate other proteolytic systems involved to SMN degradation,we also studied the effect of the inhibition of the calcium-dependent protease, calpain, on Smn protein level. Our results demonstrate that calpain reduction increases Smn and LC3-II level in cultured MNs. Collectively, these results provide new insight into the role of autophagy and its modulation in SMN protein regulation.ca_ES
dc.description.sponsorshipThisworkwas supported by grants fromInstituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, Unión Europea, Fondo europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” (PI14/ 00060), 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, NB held a contract from Instituto de Salud Carlos III (PI11/01047). We thank Elaine Lilly, Ph.D., for English language revision of the manuscript.ca_ES
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.expneurol.2016.06.032ca_ES
dc.relation.ispartofExperimental Neurology, 2016, vol. 283, p. 287–297ca_ES
dc.rights(c) Elsevier Inc, 2016ca_ES
dc.subjectSpinal Muscular Atrophyca_ES
dc.subjectMotoneuronca_ES
dc.subjectSurvival motor neuronca_ES
dc.subjectAutophagyca_ES
dc.subjectAutophagosomeca_ES
dc.subjectCalpainca_ES
dc.subjectRapamycinca_ES
dc.titleAutophagy modulators regulate survival motor neuron protein stability in motoneuronsca_ES
dc.typearticleca_ES
dc.identifier.idgrec024511
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1016/j.expneurol.2016.06.032
dc.date.embargoEndDate10000-01-01


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