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dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorVarea, Olga
dc.contributor.authorGuinovart, Joan
dc.contributor.authorDuran Castells, Jordi
dc.date.accessioned2024-11-01T14:46:47Z
dc.date.available2024-11-01T14:46:47Z
dc.date.issued2022
dc.identifier.issn2632-1297ca
dc.identifier.urihttp://hdl.handle.net/20.500.14342/4517
dc.description.abstractLafora disease is a fatal neurodegenerative childhood dementia caused by loss-of-function mutations in either the laforin or malin gene. The hallmark of the disease is the accumulation of abnormal glycogen aggregates known as Lafora bodies (LBs) in the brain and other tissues. These aggregates are responsible for the pathological features of the disease. As a monogenic disorder, Lafora disease is a good candidate for gene therapy-based approaches. However, most patients are diagnosed after the appearance of the first symptoms and thus when LBs are already present in the brain. In this context, it was not clear whether the restoration of a normal copy of the defective gene (either laforin or malin) would prove effective. Here we evaluated the effect of restoring malin in a malin-deficient mouse model of Lafora disease as a proof of concept for gene replacement therapy. To this end, we generated a malin-deficient mouse in which malin expression can be induced at a certain time. Our results reveal that malin restoration at an advanced stage of the disease arrests the accumulation of LBs in brain and muscle, induces the degradation of laforin and glycogen synthase bound to the aggregates, and ameliorates neuroinflammation. These results identify malin restoration as the first therapeutic strategy to show effectiveness when applied at advanced stages of Lafora disease.ca
dc.format.extentp.14ca
dc.language.isoengca
dc.publisherOxford University Pressca
dc.relation.ispartofBrain Communications 2022, 4(4), fcac168ca
dc.rights© L'autor/aca
dc.rightsAttribution 4.0 Internationalca
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.otherGlycogenca
dc.subject.otherLafora diseaseca
dc.subject.otherNeurodegenerationca
dc.subject.otherNeuroinflammationca
dc.subject.otherGene therapyca
dc.subject.otherGlicogenca
dc.subject.otherTeràpia genèticaca
dc.subject.otherSistema nerviós--Degeneracióca
dc.titleMalin restoration as proof of concept for gene therapy for Lafora diseaseca
dc.typeinfo:eu-repo/semantics/articleca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.subject.udc616.8ca
dc.identifier.doihttps://doi.org/10.1093/braincomms/fcac168ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/MEIC/PN I+D/BFU2017-84345-Pca
dc.relation.projectIDinfo:eu-repo/grantAgreement/MCI/PN I+D/PID2020-118699GB-I00ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/NIH/NINDS/P01NS097197ca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca


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