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dc.contributor.authorMiñano Molina, Alfredo Jesús
dc.contributor.authorEspaña, Judit
dc.contributor.authorMartín, Elsa
dc.contributor.authorBarneda-Zahonero, Bruna
dc.contributor.authorFadó Andrés, Rut
dc.contributor.authorSolé, Montse
dc.contributor.authorTrullás, Ramón
dc.contributor.authorSaura, Carlos A.
dc.contributor.authorRodríguez-Álvarez, José
dc.date.accessioned2021-05-03T16:21:58Z
dc.date.available2021-05-03T16:21:58Z
dc.date.issued2011-08-05
dc.identifier.citationMiñano-Molina, Alfredo J.; España, Judit; Martín, Elsa [et al.]. Soluble oligomers of amyloid-β peptide disrupt Membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction. Journal of Biological Chemistry, 2011, 286(31), p. 27311-27321. Disponible en: <https://www.sciencedirect.com/science/article/pii/S0021925820503372?via%3Dihub>. Fecha de acceso: 3 may. 2021. DOI: 10.1074/jbc.M111.227504ca
dc.identifier.issn0021-9258ca
dc.identifier.urihttp://hdl.handle.net/20.500.12328/2513
dc.description.abstractβ-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie the pathophysiology of Alzheimer disease (AD). Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading to cognitive failure associated with AD. The Aβ-induced synaptic dysfunction has been attributed to the synaptic removal of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs). However, the molecular mechanisms underlying the loss of AMPAR induced by Aβ at synapses are largely unknown. In this study we have examined the effect of Aβ oligomers on phosphorylated GluA1 at serine 845, a residue that plays an essential role in the trafficking of AMPARs toward extrasynaptic sites and the subsequent delivery to synapses during synaptic plasticity events. We found that Aβ oligomers reduce basal levels of Ser-845 phosphorylation and surface expression of AMPARs affecting AMPAR subunit composition. Aβ-induced GluA1 dephosphorylation and reduced receptor surface levels are mediated by an increase in calcium influx into neurons through ionotropic glutamate receptors and activation of the calcium-dependent phosphatase calcineurin. Moreover, Aβ oligomers block the extrasynaptic delivery of AMPARs induced by chemical synaptic potentiation. In addition, reduced levels of total and phosphorylated GluA1 are associated with initial spatial memory deficits in a transgenic mouse model of AD. These findings indicate that Aβ oligomers could act as a synaptic depressor affecting the mechanisms involved in the targeting of AMPARs to the synapses during early stages of the disease.en
dc.format.extent11ca
dc.language.isoengca
dc.publisherElsevierca
dc.relation.ispartofJournal of Biological Chemistryca
dc.relation.ispartofseries286;31
dc.rightsUnder a Creative Commons license. This is an Open Access article under the CC BY license.ca
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.otherAlzheimer, Malaltia d'ca
dc.subject.otherFisiologia patològicaca
dc.subject.otherNeurotransmissióca
dc.subject.otherEnfermedad de Alzheimeres
dc.subject.otherFisiopatologíaes
dc.subject.otherNeurotransmisoreses
dc.subject.otherAlzheimer's diseaseen
dc.subject.otherPathological physiologyen
dc.subject.otherNeurotransmissionen
dc.titleSoluble oligomers of amyloid-β peptide disrupt Membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunctionen
dc.typeinfo:eu-repo/semantics/otherca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/3PN/SAF2008-0190ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/3PN/SAF2010-20925ca
dc.subject.udc61ca
dc.subject.udc616.8ca
dc.identifier.doihttps://dx.doi.org/10.1074/jbc.M111.227504ca


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Under a Creative Commons license. This is an Open Access article under the CC BY license.
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