{"dcterms:modified":"2026-06-10","dcterms:creator":"Repositorio de datos de investigación de la Universidad de Chile","@type":"ore:ResourceMap","@id":"http://datos.uchile.cl/api/datasets/export?exporter=OAI_ORE&persistentId=https://doi.org/10.34691/UCHILE/4MDLCP","ore:describes":{"author":[{"citation:authorName":"Hetz, Claudio","citation:authorAffiliation":"Universidad de Chile - Facultad de Medicina","authorIdentifierScheme":"ORCID","authorIdentifier":"0000-0003-1120-7966"},{"citation:authorName":"Vicente Valenzuela","citation:authorAffiliation":"Biomedical Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile"},{"citation:authorName":"Daniela Becerra"},{"citation:authorName":"José Astorga"},{"citation:authorName":"Matias Fuentealba"},{"citation:authorName":"Guillermo Diaz"},{"citation:authorName":"Leslie Bargsted"},{"citation:authorName":"Carlos Chacón"},{"citation:authorName":"Alexis Martinez"},{"citation:authorName":"Romina Gozalvo"},{"citation:authorName":"Kasey Jackson","citation:authorAffiliation":"Sanofi Genzyme Corp., Cambridge Ma, USA"},{"citation:authorName":"Vania Morales"},{"citation:authorName":"Macarena Las Heras"},{"citation:authorName":"Giovanni Tamburini"},{"citation:authorName":"Leonard Petrucelli"},{"citation:authorName":"Pablo Sardi"},{"citation:authorName":"Lars Plate"}],"citation:dsDescription":{"citation:dsDescriptionValue":"Data used for Research Article submission to Molecular Therapy Journal for review Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting on a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress. Here we provide evidence of suboptimal activation of the UPR in ALS/FTD models under experimental ER stress. To artificially engage the UPR, we intracerebroventricularly administrated adeno-associated viruses (AAV) to express the active form of XBP1 (XBP1s) in the nervous system of ALS/FTD models. XBP1s expression improved motor performance and extended life span of mutant SOD1 mice, associated with reduced protein aggregation. AAV-XBP1s administration also attenuated disease progression in models of TDP-43 and C9orf72 pathogenesis. Proteomic profiling of spinal cord tissue revealed that XBP1s overexpression improved proteostasis and modulated the expression of a cluster of synaptic and cell morphology proteins. Our results suggest that strategies to improve ER proteostasis may serve as a pan-therapeutic strategy to treat ALS/FTD.","citation:dsDescriptionDate":"2024-05-30"},"citation:datasetContact":{"citation:datasetContactName":"Hetz, Claudio","citation:datasetContactAffiliation":"Universidad de Chile - Facultad de Medicina","citation:datasetContactEmail":"chetz@uchile.cl"},"citation:depositor":"Hetz, Claudio","subject":"Medicine, Health and Life Sciences","dateOfDeposit":"2024-05-30","title":"Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.","@id":"https://doi.org/10.34691/UCHILE/4MDLCP","@type":["ore:Aggregation","schema:Dataset"],"schema:version":"2.0","schema:name":"Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.","schema:dateModified":"Thu May 30 10:29:34 CLT 2024","schema:datePublished":"2024-05-30","schema:license":"http://creativecommons.org/licenses/by/4.0","dvcore:fileTermsOfAccess":{"dvcore:fileRequestAccess":true},"schema:includedInDataCatalog":"Repositorio de datos de investigación de la Universidad de Chile","schema:isPartOf":{"schema:name":"Facultad de Medicina","@id":"http://datos.uchile.cl/dataverse/FM","schema:isPartOf":{"schema:name":"Repositorio de datos de investigación de la Universidad de Chile","@id":"http://datos.uchile.cl/dataverse/uchile","schema:description":"The root dataverse."}},"ore:aggregates":[{"schema:name":"Valenzuela et al. 2024 Figures Mol Ther_FINAL-1.pdf","dvcore:restricted":false,"schema:version":1,"dvcore:datasetVersionId":426,"@id":"doi:10.34691/UCHILE/4MDLCP/K2H1P4","schema:sameAs":"http://datos.uchile.cl/api/access/datafile/:persistentId?persistentId=doi:10.34691/UCHILE/4MDLCP/K2H1P4","@type":"ore:AggregatedResource","schema:fileFormat":"application/pdf","dvcore:filesize":212497,"dvcore:storageIdentifier":"file://18fc9e769dc-57ed7db986cd","dvcore:rootDataFileId":-1,"dvcore:checksum":{"@type":"MD5","@value":"db52ede429bd95866288f502db35a4a1"}}],"schema:hasPart":["doi:10.34691/UCHILE/4MDLCP/K2H1P4"]},"@context":{"author":"http://purl.org/dc/terms/creator","authorIdentifier":"http://purl.org/spar/datacite/AgentIdentifier","authorIdentifierScheme":"http://purl.org/spar/datacite/AgentIdentifierScheme","citation":"https://dataverse.org/schema/citation/","dateOfDeposit":"http://purl.org/dc/terms/dateSubmitted","dcterms":"http://purl.org/dc/terms/","dvcore":"https://dataverse.org/schema/core#","ore":"http://www.openarchives.org/ore/terms/","schema":"http://schema.org/","subject":"http://purl.org/dc/terms/subject","title":"http://purl.org/dc/terms/title"}}