ALS-linked protein disulfide isomerase variants cause motor dysfunction

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dc.contributor.authorWoehlbier, Ute
dc.contributor.authorColombo, Alicia
dc.contributor.authorSaaranen, Mirva J
dc.contributor.authorPérez, Viviana
dc.contributor.authorOjeda, Jorge
dc.contributor.authorBustos, Fernando J.
dc.contributor.authorAndreu, Catherine I.
dc.contributor.authorTorres, Mauricio
dc.contributor.authorValenzuela, Vicente
dc.contributor.authorMedinas, Danilo B
dc.contributor.authorRozas, Pablo
dc.contributor.authorVidal, Rene L.
dc.contributor.authorLopez-Gonzalez, Rodrigo
dc.contributor.authorSalameh, Johnny
dc.contributor.authorFernandez-Collemann, Sara
dc.contributor.authorMuñoz, Natalia
dc.contributor.authorMatus, Soledad
dc.contributor.authorArmisen, Ricardo
dc.contributor.authorSagredo, Alfredo
dc.contributor.authorPalma, Karina
dc.contributor.authorIrrazabal, Thergiory
dc.contributor.authorAlmeida, Sandra
dc.contributor.authorGonzalez-Perez, Paloma
dc.contributor.authorCampero, Mario
dc.contributor.authorGao, Fen-Biao
dc.contributor.authorHenny, Pablo
dc.contributor.authorVan Zundert, Brigitte
dc.contributor.authorRuddock, Lloyd W
dc.contributor.authorConcha, Miguel L
dc.contributor.authorHenriquez, Juan P.
dc.contributor.authorBrown, Robert H.
dc.contributor.authorHetz, Claudio
dc.date.accessioned2023-11-09T19:25:54Z
dc.date.available2023-11-09T19:25:54Z
dc.date.issued2016-04
dc.descriptionIndexación: Scopus.es
dc.description.abstractDisturbance of endoplasmic reticulum (ER) proteostasis is a common feature of amyotrophic lateral sclerosis (ALS). Protein disulfide isomerases (PDIs) are ER foldases identified as possible ALS biomarkers, as well as neuroprotective factors. However, no functional studies have addressed their impact on the disease process. Here, we functionally characterized four ALS-linked mutations recently identified in two major PDI genes, PDIA1 and PDIA3/ERp57. Phenotypic screening in zebrafish revealed that the expression of these PDI variants induce motor defects associated with a disruption of motoneuron connectivity. Similarly, the expression of mutant PDIs impaired dendritic outgrowth in motoneuron cell culture models. Cellular and biochemical studies identified distinct molecular defects underlying the pathogenicity of these PDI mutants. Finally, targeting ERp57 in the nervous system led to severe motor dysfunction in mice associated with a loss of neuromuscular synapses. This study identifies ER proteostasis imbalance as a risk factor for ALS, driving initial stages of the disease.es
dc.description.urihttps://www.embopress.org/doi/full/10.15252/embj.201592224
dc.identifier.citationWiley-VCH Verlages
dc.identifier.issn02614-189
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/53881
dc.language.isoenes
dc.publisherEMBO Journal. Volume 35, Issue 8, Pages 845 - 865. 15 April 2016es
dc.subjectAmyotrophic Lateral Sclerosises
dc.subjectERp57es
dc.subjectPDIA1es
dc.subjectProtein Disulfide Isomerasees
dc.titleALS-linked protein disulfide isomerase variants cause motor dysfunctiones
dc.typeArtículoes
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