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dc.creatorWoehlbier, Ute
dc.creatorColombo, Alicia
dc.creatorSaaranen, Mirva J
dc.creatorPérez, Viviana
dc.creatorOjeda, Jorge
dc.creatorBustos, Fernando J
dc.creatorAndreu, Catherine I
dc.creatorTorres, Mauricio
dc.creatorValenzuela, Vicente
dc.creatorMedinas, Danilo B
dc.creatorRozas, Pablo
dc.creatorVidal, René L
dc.creatorLópez-González, Rodrigo
dc.creatorSalameh, Johnny
dc.creatorFernández-Collemann, Sara
dc.creatorMuñoz, Natalia
dc.creatorMatus, Soledad
dc.creatorArmisen-Yáñez, Ricardo Amado
dc.creatorSagredo, Alfredo
dc.creatorPalma, Karina
dc.creatorIrrazabal, Thergiory
dc.creatorAlmeida, Sandra
dc.creatorGonzález-Pérez, Paloma
dc.creatorCampero, Mario
dc.creatorGao, Fen-Biao
dc.creatorHenny, Pablo
dc.creatorvan Zundert, Brigitte
dc.creatorRuddock, Lloyd W
dc.creatorConcha, Miguel L
dc.creatorHenríquez, Juan P
dc.creatorBrown, Robert H
dc.creatorHetz, Claudio
dc.date.accessioned2021-08-23T22:51:07Z
dc.date.available2021-08-23T22:51:07Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/10533/250728
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.
dc.language.isoeng
dc.relation.urihttps://doi.org/10.15252/embj.201592224
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.titleALS-linked protein disulfide isomerase variants cause motor dysfunction
dc.typeArticulo
dc.description.conicytinstrumentRegular 2015
dc.identifier.folio1150743
dc.description.conicytprogramFONDECYT
dc.relation.contesthandle/10533/111557
dc.rights.driverinfo:eu-repo/semantics/article
dc.rights.driverinfo:eu-repo/semantics/openAccess
dc.title.journalEMBO JOURNAL
dc.relation.instrumenthandle/10533/111541
dc.relation.programhandle/10533/108045
dc.description.shortconicytprogramFONDECYT
dc.type.openaireinfo:eu-repo/semantics/publishedVersion


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