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dc.rights.licenseopenen_US
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorLOPEZ-CUINA, Miguel
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorGUÉRIN, Paul
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorDUTHEIL, Nathalie
hal.structure.identifierInterdisciplinary Institute for Neuroscience / Institut interdisciplinaire de neurosciences [Bordeaux] [IINS]
dc.contributor.authorMARTIN, Christelle
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorLESTE-LASSERRE, Thierry
hal.structure.identifierLaboratoire de neurosciences expérimentales et cliniques [LNEC [Poitiers]]
dc.contributor.authorFERNAGUT, Pierre‐olivier
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorMEISSNER, Wassilios
IDREF: 113664761
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorBEZARD, Erwan
dc.date.accessioned2024-01-09T11:11:29Z
dc.date.available2024-01-09T11:11:29Z
dc.date.issued2023-07
dc.identifier.issn0885-3185en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/186974
dc.description.abstractEnAbstract Background Multiple system atrophy (MSA) is a sporadic adult‐onset rare neurodegenerative synucleinopathy for which counteracting central nervous system insulin resistance bears the potential of being neuroprotective. G‐protein‐(heterotrimeric guanine nucleotide‐binding protein)‐coupled receptor kinase 2 (GRK2) is emerging as a physiologically relevant inhibitor of insulin signaling. Objectives We tested whether lowering brain GRK2 abundance may reverse insulin‐resistance. Methods We lowered brain GRK2 abundance through viral‐mediated delivery of a GRK2‐specific miRNA and quantified the reversion of a developing or an established insulin‐resistant phenotype using the transgenic PLP‐SYN mouse model of MSA. Results Viral vector delivery of a GRK2 miRNA demonstrated a neuroprotective capacity when administered (1) in utero intracerebroventricularly in developing PLP‐SYN mice and (2) intrastriatally in adult PLP‐SYN mice. Decreased striatal GRK2 levels correlated in both designs with neuroprotection of the substantia nigra dopamine neurons, reduction in high‐molecular‐weight species of α‐synuclein, and reduced insulin resistance. Conclusions These data support GRK2 as a potential therapeutic target in MSA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enInsulin resistance
dc.subject.enSynucleinopathy
dc.subject.enIn utero
dc.title.enGRK2‐ Targeted Knockdown as Therapy for Multiple System Atrophy
dc.title.alternativeMov Disorden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/mds.29422en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37093618en_US
bordeaux.journalMovement Disordersen_US
bordeaux.page1336-1340en_US
bordeaux.volume38en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.institutionINSERMen_US
bordeaux.teamTranscriptomeen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDAssociation France Alzheimeren_US
bordeaux.identifier.funderIDAssociation France Parkinsonen_US
bordeaux.import.sourcehal
hal.identifierhal-04234640
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Movement%20Disorders&rft.date=2023-07&rft.volume=38&rft.issue=7&rft.spage=1336-1340&rft.epage=1336-1340&rft.eissn=0885-3185&rft.issn=0885-3185&rft.au=LOPEZ-CUINA,%20Miguel&GU%C3%89RIN,%20Paul&DUTHEIL,%20Nathalie&MARTIN,%20Christelle&LESTE-LASSERRE,%20Thierry&rft.genre=article


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