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dc.contributor.authorCunha Alves, Victoria
dc.contributor.authorFigueiro-Silva, Joana
dc.contributor.authorFerrer, Isidoro
dc.contributor.authorCarro, Eva 
dc.date.accessioned2023-09-27T07:46:17Z
dc.date.available2023-09-27T07:46:17Z
dc.date.issued2023-07-05
dc.identifier.citationCell Mol Life Sci. 2023 Jul 5;80(8):196.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/16515
dc.description.abstractModulation of brain olfactory (OR) and taste receptor (TASR) expression was recently reported in neurological diseases. However, there is still limited evidence of these genes' expression in the human brain and the transcriptional regulation mechanisms involved remain elusive. We explored the possible expression and regulation of selected OR and TASR in the human orbitofrontal cortex (OFC) of sporadic Alzheimer's disease (AD) and non-demented control specimens using quantitative real-time RT-PCR and ELISA. Global H3K9me3 amounts were measured on OFC total histone extracts, and H3K9me3 binding at each chemoreceptor locus was examined through native chromatin immunoprecipitation. To investigate the potential interactome of the repressive histone mark H3K9me3 in OFC specimens, native nuclear complex co-immunoprecipitation (Co-IP) was combined with reverse phase-liquid chromatography coupled to mass spectrometry analysis. Interaction between H3K9me3 and MeCP2 was validated by reciprocal Co-IP, and global MeCP2 levels were quantitated. We found that OR and TAS2R genes are expressed and markedly downregulated in OFC at early stages of sporadic AD, preceding the progressive reduction in their protein levels and the appearance of AD-associated neuropathology. The expression pattern did not follow disease progression suggesting transcriptional regulation through epigenetic mechanisms. We discovered an increase of OFC global H3K9me3 levels and a substantial enrichment of this repressive signature at ORs and TAS2Rs proximal promoter at early stages of AD, ultimately lost at advanced stages. We revealed the interaction between H3K9me3 and MeCP2 at early stages and found that MeCP2 protein is increased in sporadic AD. Findings suggest MeCP2 might be implicated in OR and TAS2R transcriptional regulation through interaction with H3K9me3, and as an early event, it may uncover a novel etiopathogenetic mechanism of sporadic AD.es_ES
dc.description.sponsorshipThis research was supported by grants from Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), CIBERNED (CB07/502, PI2021/03), and FEDER. The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherSpringer es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAlzheimer’s diseasees_ES
dc.subjectHistone methylationes_ES
dc.subjectMeCP2es_ES
dc.subjectOlfactory receptorses_ES
dc.subjectOrbitofrontal cortexes_ES
dc.subjectTaste receptorses_ES
dc.subject.meshAlzheimer Disease es_ES
dc.subject.meshHumans es_ES
dc.subject.meshGene Expression es_ES
dc.subject.meshEpigenesis, Genetices_ES
dc.subject.meshHistones es_ES
dc.subject.meshPrefrontal Cortex es_ES
dc.titleEpigenetic silencing of OR and TAS2R genes expression in human orbitofrontal cortex at early stages of sporadic Alzheimer's diseasees_ES
dc.typeresearch articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID37405535es_ES
dc.format.volume80es_ES
dc.format.number8es_ES
dc.format.page196es_ES
dc.identifier.doi10.1007/s00018-023-04845-1es_ES
dc.contributor.funderComunidad de Madrid (España) es_ES
dc.contributor.funderCentro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas) es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1420-9071es_ES
dc.relation.publisherversionhttps://doi.org/10.1007/s00018-023-04845-1es_ES
dc.identifier.journalCellular and molecular life sciences : CMLSes_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/PI2021/03es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/CB07/502es_ES


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