N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers

dc.creatorDecker, Helena
dc.creatorJürgensen, Sofia
dc.creatorAdrover, Martín Federico
dc.creatorBrito Moreira, Jordano
dc.creatorBomfim, Theresa R.
dc.creatorKlein, William L.
dc.creatorEpstein, Alberto L.
dc.creatorDe Felice, Fernanda G.
dc.creatorJerusalinsky, Diana Alicia
dc.creatorFerreira, Sergio Teixeira
dc.date2010-12
dc.date.accessioned2023-08-31T00:11:13Z
dc.date.available2023-08-31T00:11:13Z
dc.identifierhttp://hdl.handle.net/11336/193100
dc.identifierDecker, Helena; Jürgensen, Sofia; Adrover, Martín Federico; Brito Moreira, Jordano; Bomfim, Theresa R.; et al.; N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 115; 6; 12-2010; 1520-1529
dc.identifier0022-3042
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8543191
dc.descriptionSoluble amyloid-b peptide (Ab) oligomers, known to accumulate in Alzheimer´s disease brains, target excitatory post-synaptic terminals. This is thought to trigger synapse deterioration, a mechanism possibly underlying memory loss in early stage Alzheimer´s disease. A major unknown is the identity of the receptor(s) targeted by oligomers at synapses. Because oligomers have been shown to interfere with N-methyl-D-aspartate receptor (NMDAR) function and trafficking, we hypothesized that NMDARs might be required for oligomer binding to synapses. An amplicon vector was used to knock-down NMDARs in mature hippocampal neurons in culture, yielding 90% reduction in dendritic NMDAR expression and blocking neuronal oxidative stress induced by Ab oligomers, a pathological response that has been shown to be mediated by NMDARs. Remarkably, NMDAR knock-down abolished oligomer binding to dendrites, indicating that NMDARs are required for synaptic targeting of oligomers. Nevertheless, oligomers do not appearto bind directly to NMDARs as indicated by the fact that both oligomer-attacked and non-attacked neurons exhibit similar surface levels of NMDARs. Furthermore, pre-treatment of neurons with insulin down-regulates oligomer-binding sites in the absence of a parallel reduction in surface levels of NMDARs. Establishing that NMDARs are key components of the synaptic oligomer binding complex may illuminate the development of novel approaches to prevent synapse failure triggered by Ab oligomers.
dc.descriptionFil: Decker, Helena. Universidade Federal do Rio de Janeiro; Brasil
dc.descriptionFil: Jürgensen, Sofia. Universidade Federal do Rio de Janeiro; Brasil
dc.descriptionFil: Adrover, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
dc.descriptionFil: Brito Moreira, Jordano. Universidade Federal do Rio de Janeiro; Brasil
dc.descriptionFil: Bomfim, Theresa R.. Universidade Federal do Rio de Janeiro; Brasil
dc.descriptionFil: Klein, William L.. Northwestern University; Estados Unidos
dc.descriptionFil: Epstein, Alberto L.. Universite Claude Bernard Lyon 1. Institut de Physique Nucléaire de Lyon.; Francia
dc.descriptionFil: De Felice, Fernanda G.. Universidade Federal do Rio de Janeiro; Brasil
dc.descriptionFil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
dc.descriptionFil: Ferreira, Sergio Teixeira. Universidade Federal do Rio de Janeiro; Brasil
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley Blackwell Publishing, Inc
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/ 10.1111/j.1471-4159.2010.07058.x
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subjectALZHEIMER'S DISEASE
dc.subjectAΒ OLIGOMERS
dc.subjectINSULIN
dc.subjectNMDA RECEPTOR
dc.subjectSYNAPSE DYSFUNCTION
dc.subjecthttps://purl.org/becyt/ford/1.6
dc.subjecthttps://purl.org/becyt/ford/1
dc.titleN-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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