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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSansa, Alba
dc.contributor.authorHidalgo, Ivan
dc.contributor.authorMiralles, Maria P.
dc.contributor.authorde la Fuente, Sandra
dc.contributor.authorPérez García, Maria Jose
dc.contributor.authorMunell Casadesus, Francina
dc.date.accessioned2022-04-07T12:17:15Z
dc.date.available2022-04-07T12:17:15Z
dc.date.issued2021-07-03
dc.identifier.citationSansa A, Hidalgo I, Miralles MP, de la Fuente S, Perez-Garcia MJ, Munell F, et al. Spinal Muscular Atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons. Acta Neuropathol Commun. 2021 Jul 3;9:122.
dc.identifier.issn2051-5960
dc.identifier.urihttp://hdl.handle.net/11351/7328
dc.descriptionMotoneuron; Neurodegeneration; Neuromuscular disease
dc.description.abstractSpinal muscular atrophy (SMA) is a neuromuscular genetic disease caused by reduced survival motor neuron (SMN) protein. SMN is ubiquitous and deficient levels cause spinal cord motoneurons (MNs) degeneration and muscle atrophy. Nevertheless, the mechanism by which SMN reduction in muscle contributes to SMA disease is not fully understood. Therefore, studies evaluating atrophy mechanisms in SMA muscles will contribute to strengthening current knowledge of the pathology. Here we propose to evaluate autophagy in SMA muscle, a pathway altered in myotube atrophy. We analized autophagy proteins and mTOR in muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients and in gastrocnemius muscles from a severe SMA mouse model. Human MNs differentiated from SMA and unaffected control iPSCs were also included in the analysis of the autophagy. Muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients showed reduction of the autophagy marker LC3-II. In SMA mouse gastrocnemius, we observed lower levels of LC3-II, Beclin 1, and p62/SQSTM1 proteins at pre-symptomatic stage. mTOR phosphorylation at Ser2448 was decreased in SMA muscle cells. However, in mouse and human cultured SMA MNs mTOR phosphorylation and LC3-II levels were increased. These results suggest a differential regulation in SMA of the autophagy process in muscle cells and MNs. Opposite changes in autophagy proteins and mTOR phosphorylation between muscle cells and neurons were observed. These differences may reflect a specific response to SMN reduction, which could imply diverse tissue-dependent reactions to therapies that should be taken into account when treating SMA patients.
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofseriesActa Neuropathologica Communications;9
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectAtròfia muscular espinal - Patogènesi
dc.subjectAutofàgia - Patogènesi
dc.subjectMúscul estriat - Patogènesi
dc.subject.meshMuscular Atrophy, Spinal
dc.subject.meshMuscle, Skeletal
dc.subject.meshAutophagy
dc.titleSpinal Muscular Atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1186/s40478-021-01223-5
dc.subject.decsatrofia muscular espinal
dc.subject.decsmúsculo esquelético
dc.subject.decsautofagia
dc.relation.publishversionhttps://doi.org/10.1186/s40478-021-01223-5
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Sansa A, Hidalgo I, Miralles MP, de la Fuente S] Neuronal Signaling Unit, Experimental Medicine Department, Universitat de Lleida-IRBLleida, 25198 Lleida, Spain. [Perez-Garcia MJ, Munell F] Grup de Recerca en Neurologia Pediàtrica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Trastorns Neuromusculars Pediàtrics, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid34217376
dc.identifier.wos000669285200001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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