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dc.contributor.authorBerthier, Arnaudes_ES
dc.contributor.authorPaya, Migueles_ES
dc.contributor.authorGarcia-Cabrero, A.Mes_ES
dc.contributor.authorBallester, María Inmaculadaes_ES
dc.contributor.authorHeredia, Migueles_ES
dc.contributor.authorSerratosa, J.Mes_ES
dc.contributor.authorSanchez, M.Pes_ES
dc.contributor.authorSanz, Pascuales_ES
dc.date.accessioned2016-03-22T12:55:03Z-
dc.date.available2016-03-22T12:55:03Z-
dc.date.issued2015-01-28-
dc.identifier.citationMolecular Neurobiology 53(2):1296-309. (2016)es_ES
dc.identifier.issn0893-7648-
dc.identifier.urihttp://hdl.handle.net/10261/130371-
dc.description14 páginas; 9 figuras.es_ES
dc.description.abstractLafora disease (LD, OMIM 254780) is a rare fatal neurodegenerative disorder that usually occurs during childhood with generalized tonic-clonic seizures, myoclonus, absences, drop attacks or visual seizures. Unfortunately, at present, available treatments are only palliatives and no curative drugs are available yet. The hallmark of the disease is the accumulation of insoluble polyglucosan inclusions, called Lafora bodies (LBs), within the neurons but also in heart, muscle and liver cells. Mouse models lacking functional EPM2A or EPM2B genes (the two major loci related to the disease) recapitulate the Lafora disease phenotype: they accumulate polyglucosan inclusions, show signs of neurodegeneration and have a dysregulation of protein clearance and endoplasmic reticulum stress response. In this study, we have subjected a mouse model of LD (Epm2b-/-) to different pharmacological interventions aimed to alleviate protein clearance and endoplasmic reticulum stress. We have used two chemical chaperones, trehalose and 4-phenylbutyric acid. In addition, we have used metformin, an activator of AMP-activated protein kinase (AMPK), as it has a recognized neuroprotective role in other neurodegenerative diseases. Here, we show that treatment with 4-phenylbutyric acid or metformin decreases the accumulation of Lafora bodies and polyubiquitin protein aggregates in the brain of treated animals. 4-Phenylbutyric acid and metformin also diminish neurodegeneration (measured in terms of neuronal loss and reactive gliosis) and ameliorate neuropsychological tests of Epm2b-/- mice. As these compounds have good safety records and are already approved for clinical uses on different neurological pathologies, we think that the translation of our results to the clinical practice could be straightforward.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Education and Science SAF2011-27442, Fundació La Marato de TV3 (ref. 100130) and an ACCI2012 action from CIBERER. A.B. holds a postdoctoral fellowship from the Program “Junta para la Ampliación de Estudios” (JAE-Doc) co-funded by the European Social Fund (ESF).es_ES
dc.language.isoenges_ES
dc.publisherSpringer Naturees_ES
dc.relation.isversionofPostprintes_ES
dc.rightsopenAccesses_ES
dc.subjectLafora diseasees_ES
dc.subjectPolyglucosan accumulationes_ES
dc.subjectMetformines_ES
dc.subject4-phenylbutyric acides_ES
dc.subjectTrehalosees_ES
dc.subjectPharmacological interventiones_ES
dc.titlePharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Diseasees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1007/s12035-015-9091-8-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1007/s12035-015-9091-8es_ES
dc.identifier.e-issn1559-1182-
dc.contributor.funderMinisterio de Educación y Ciencia (España)es_ES
dc.contributor.funderFundació La Marató de TV3es_ES
dc.contributor.funderEuropean Science Foundationes_ES
dc.relation.csices_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100008666es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000782es_ES
dc.identifier.pmid25627694-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
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