{"@context":"http://schema.org","@type":"Dataset","@id":"https://doi.org/10.34691/UCHILE/4MDLCP","identifier":"https://doi.org/10.34691/UCHILE/4MDLCP","name":"Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.","creator":[{"@type":"Person","givenName":"Claudio","familyName":"Hetz","affiliation":{"@type":"Organization","name":"Universidad de Chile - Facultad de Medicina"},"sameAs":"https://orcid.org/0000-0003-1120-7966","@id":"https://orcid.org/0000-0003-1120-7966","identifier":"https://orcid.org/0000-0003-1120-7966","name":"Hetz, Claudio"},{"@type":"Person","givenName":"Vicente","familyName":"Valenzuela","affiliation":{"@type":"Organization","name":"Biomedical Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile"},"name":"Vicente Valenzuela"},{"@type":"Person","givenName":"Daniela","familyName":"Becerra","name":"Daniela Becerra"},{"@type":"Person","givenName":"José","familyName":"Astorga","name":"José Astorga"},{"@type":"Person","givenName":"Matias","familyName":"Fuentealba","name":"Matias Fuentealba"},{"@type":"Person","givenName":"Guillermo","familyName":"Diaz","name":"Guillermo Diaz"},{"@type":"Person","givenName":"Leslie","familyName":"Bargsted","name":"Leslie Bargsted"},{"@type":"Person","givenName":"Carlos","familyName":"Chacón","name":"Carlos Chacón"},{"@type":"Person","givenName":"Alexis","familyName":"Martinez","name":"Alexis Martinez"},{"@type":"Person","givenName":"Romina","familyName":"Gozalvo","name":"Romina Gozalvo"},{"@type":"Person","givenName":"Kasey","familyName":"Jackson","affiliation":{"@type":"Organization","name":"Sanofi Genzyme Corp., Cambridge Ma, USA"},"name":"Kasey Jackson"},{"@type":"Person","givenName":"Vania","familyName":"Morales","name":"Vania Morales"},{"@type":"Person","givenName":"Macarena","familyName":"Las Heras","name":"Macarena Las Heras"},{"@type":"Person","givenName":"Giovanni","familyName":"Tamburini","name":"Giovanni Tamburini"},{"@type":"Person","givenName":"Leonard","familyName":"Petrucelli","name":"Leonard Petrucelli"},{"@type":"Person","givenName":"Pablo","familyName":"Sardi","name":"Pablo Sardi"},{"@type":"Person","givenName":"Lars","familyName":"Plate","name":"Lars Plate"}],"author":[{"@type":"Person","givenName":"Claudio","familyName":"Hetz","affiliation":{"@type":"Organization","name":"Universidad de Chile - Facultad de Medicina"},"sameAs":"https://orcid.org/0000-0003-1120-7966","@id":"https://orcid.org/0000-0003-1120-7966","identifier":"https://orcid.org/0000-0003-1120-7966","name":"Hetz, Claudio"},{"@type":"Person","givenName":"Vicente","familyName":"Valenzuela","affiliation":{"@type":"Organization","name":"Biomedical Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile"},"name":"Vicente Valenzuela"},{"@type":"Person","givenName":"Daniela","familyName":"Becerra","name":"Daniela Becerra"},{"@type":"Person","givenName":"José","familyName":"Astorga","name":"José Astorga"},{"@type":"Person","givenName":"Matias","familyName":"Fuentealba","name":"Matias Fuentealba"},{"@type":"Person","givenName":"Guillermo","familyName":"Diaz","name":"Guillermo Diaz"},{"@type":"Person","givenName":"Leslie","familyName":"Bargsted","name":"Leslie Bargsted"},{"@type":"Person","givenName":"Carlos","familyName":"Chacón","name":"Carlos Chacón"},{"@type":"Person","givenName":"Alexis","familyName":"Martinez","name":"Alexis Martinez"},{"@type":"Person","givenName":"Romina","familyName":"Gozalvo","name":"Romina Gozalvo"},{"@type":"Person","givenName":"Kasey","familyName":"Jackson","affiliation":{"@type":"Organization","name":"Sanofi Genzyme Corp., Cambridge Ma, USA"},"name":"Kasey Jackson"},{"@type":"Person","givenName":"Vania","familyName":"Morales","name":"Vania Morales"},{"@type":"Person","givenName":"Macarena","familyName":"Las Heras","name":"Macarena Las Heras"},{"@type":"Person","givenName":"Giovanni","familyName":"Tamburini","name":"Giovanni Tamburini"},{"@type":"Person","givenName":"Leonard","familyName":"Petrucelli","name":"Leonard Petrucelli"},{"@type":"Person","givenName":"Pablo","familyName":"Sardi","name":"Pablo Sardi"},{"@type":"Person","givenName":"Lars","familyName":"Plate","name":"Lars Plate"}],"datePublished":"2024-05-30","dateModified":"2024-05-30","version":"2","description":"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.","keywords":["Medicine, Health and Life Sciences"],"license":"http://creativecommons.org/licenses/by/4.0","includedInDataCatalog":{"@type":"DataCatalog","name":"Repositorio de datos de investigación de la Universidad de Chile","url":"http://datos.uchile.cl"},"publisher":{"@type":"Organization","name":"Repositorio de datos de investigación de la Universidad de Chile"},"provider":{"@type":"Organization","name":"Repositorio de datos de investigación de la Universidad de Chile"},"distribution":[{"@type":"DataDownload","name":"Valenzuela et al. 2024 Figures Mol Ther_FINAL-1.pdf","encodingFormat":"application/pdf","contentSize":212497,"@id":"https://doi.org/10.34691/UCHILE/4MDLCP/K2H1P4","identifier":"https://doi.org/10.34691/UCHILE/4MDLCP/K2H1P4","contentUrl":"http://datos.uchile.cl/api/access/datafile/1574"}]}