GRK2‐ Targeted Knockdown as Therapy for Multiple System Atrophy
| dc.rights.license | open | en_US |
| hal.structure.identifier | Institut des Maladies Neurodégénératives [Bordeaux] [IMN] | |
| dc.contributor.author | LOPEZ-CUINA, Miguel | |
| hal.structure.identifier | Institut des Maladies Neurodégénératives [Bordeaux] [IMN] | |
| dc.contributor.author | GUÉRIN, Paul | |
| hal.structure.identifier | Institut des Maladies Neurodégénératives [Bordeaux] [IMN] | |
| dc.contributor.author | DUTHEIL, Nathalie | |
| hal.structure.identifier | Interdisciplinary Institute for Neuroscience [Bordeaux] [IINS] | |
| dc.contributor.author | MARTIN, Christelle | |
| hal.structure.identifier | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB] | |
| dc.contributor.author | LESTE-LASSERRE, Thierry | |
| hal.structure.identifier | Laboratoire de neurosciences expérimentales et cliniques [LNEC [Poitiers]] | |
| dc.contributor.author | FERNAGUT, Pierre‐olivier | |
| hal.structure.identifier | Institut des Maladies Neurodégénératives [Bordeaux] [IMN] | |
| dc.contributor.author | MEISSNER, Wassilios
IDREF: 113664761 | |
| hal.structure.identifier | Institut des Maladies Neurodégénératives [Bordeaux] [IMN] | |
| dc.contributor.author | BEZARD, Erwan | |
| dc.date.accessioned | 2024-01-09T11:11:29Z | |
| dc.date.available | 2024-01-09T11:11:29Z | |
| dc.date.issued | 2023-07 | |
| dc.identifier.issn | 0885-3185 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/186974 | |
| dc.description.abstractEn | Abstract 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.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject.en | Insulin resistance | |
| dc.subject.en | Synucleinopathy | |
| dc.subject.en | In utero | |
| dc.title.en | GRK2‐ Targeted Knockdown as Therapy for Multiple System Atrophy | |
| dc.title.alternative | Mov Disord | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1002/mds.29422 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 37093618 | en_US |
| bordeaux.journal | Movement Disorders | en_US |
| bordeaux.page | 1336-1340 | en_US |
| bordeaux.volume | 38 | en_US |
| bordeaux.hal.laboratories | Neurocentre Magendie - U1215 | en_US |
| bordeaux.issue | 7 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.team | Transcriptome | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Association France Alzheimer | en_US |
| bordeaux.identifier.funderID | Association France Parkinson | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-04234640 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | CC BY-NC-ND | en_US |
| bordeaux.COinS | ctx_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 |
