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

Autores
Decker, Helena; Jürgensen, Sofia; Adrover, Martín Federico; Brito Moreira, Jordano; Bomfim, Theresa R.; Klein, William L.; Epstein, Alberto L.; De Felice, Fernanda G.; Jerusalinsky, Diana Alicia; Ferreira, Sergio Teixeira
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Soluble 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.
Fil: Decker, Helena. Universidade Federal do Rio de Janeiro; Brasil
Fil: Jürgensen, Sofia. Universidade Federal do Rio de Janeiro; Brasil
Fil: 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
Fil: Brito Moreira, Jordano. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bomfim, Theresa R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Klein, William L.. Northwestern University; Estados Unidos
Fil: Epstein, Alberto L.. Universite Claude Bernard Lyon 1. Institut de Physique Nucléaire de Lyon.; Francia
Fil: De Felice, Fernanda G.. Universidade Federal do Rio de Janeiro; Brasil
Fil: 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
Fil: Ferreira, Sergio Teixeira. Universidade Federal do Rio de Janeiro; Brasil
Materia
ALZHEIMER'S DISEASE
AΒ OLIGOMERS
INSULIN
NMDA RECEPTOR
SYNAPSE DYSFUNCTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/193100
Acceder
id CONICETDig_fc4154bd34cb2447a782789f5537082a
oai_identifier_str oai:ri.conicet.gov.ar:11336/193100
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomersDecker, HelenaJürgensen, SofiaAdrover, Martín FedericoBrito Moreira, JordanoBomfim, Theresa R.Klein, William L.Epstein, Alberto L.De Felice, Fernanda G.Jerusalinsky, Diana AliciaFerreira, Sergio TeixeiraALZHEIMER'S DISEASEAΒ OLIGOMERSINSULINNMDA RECEPTORSYNAPSE DYSFUNCTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Soluble 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.Fil: Decker, Helena. Universidade Federal do Rio de Janeiro; BrasilFil: Jürgensen, Sofia. Universidade Federal do Rio de Janeiro; BrasilFil: 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; ArgentinaFil: Brito Moreira, Jordano. Universidade Federal do Rio de Janeiro; BrasilFil: Bomfim, Theresa R.. Universidade Federal do Rio de Janeiro; BrasilFil: Klein, William L.. Northwestern University; Estados UnidosFil: Epstein, Alberto L.. Universite Claude Bernard Lyon 1. Institut de Physique Nucléaire de Lyon.; FranciaFil: De Felice, Fernanda G.. Universidade Federal do Rio de Janeiro; BrasilFil: 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; ArgentinaFil: Ferreira, Sergio Teixeira. Universidade Federal do Rio de Janeiro; BrasilWiley Blackwell Publishing, Inc2010-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/193100Decker, 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; 1520-15290022-3042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/ 10.1111/j.1471-4159.2010.07058.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:21:44Zoai:ri.conicet.gov.ar:11336/193100instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:21:44.342CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
title N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
spellingShingle N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
Decker, Helena
ALZHEIMER'S DISEASE
AΒ OLIGOMERS
INSULIN
NMDA RECEPTOR
SYNAPSE DYSFUNCTION
title_short N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
title_full N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
title_fullStr N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
title_full_unstemmed N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
title_sort N-Methyl-d-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers
dc.creator.none.fl_str_mv Decker, Helena
Jürgensen, Sofia
Adrover, Martín Federico
Brito Moreira, Jordano
Bomfim, Theresa R.
Klein, William L.
Epstein, Alberto L.
De Felice, Fernanda G.
Jerusalinsky, Diana Alicia
Ferreira, Sergio Teixeira
author Decker, Helena
author_facet Decker, Helena
Jürgensen, Sofia
Adrover, Martín Federico
Brito Moreira, Jordano
Bomfim, Theresa R.
Klein, William L.
Epstein, Alberto L.
De Felice, Fernanda G.
Jerusalinsky, Diana Alicia
Ferreira, Sergio Teixeira
author_role author
author2 Jürgensen, Sofia
Adrover, Martín Federico
Brito Moreira, Jordano
Bomfim, Theresa R.
Klein, William L.
Epstein, Alberto L.
De Felice, Fernanda G.
Jerusalinsky, Diana Alicia
Ferreira, Sergio Teixeira
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALZHEIMER'S DISEASE
AΒ OLIGOMERS
INSULIN
NMDA RECEPTOR
SYNAPSE DYSFUNCTION
topic ALZHEIMER'S DISEASE
AΒ OLIGOMERS
INSULIN
NMDA RECEPTOR
SYNAPSE DYSFUNCTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Soluble 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.
Fil: Decker, Helena. Universidade Federal do Rio de Janeiro; Brasil
Fil: Jürgensen, Sofia. Universidade Federal do Rio de Janeiro; Brasil
Fil: 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
Fil: Brito Moreira, Jordano. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bomfim, Theresa R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Klein, William L.. Northwestern University; Estados Unidos
Fil: Epstein, Alberto L.. Universite Claude Bernard Lyon 1. Institut de Physique Nucléaire de Lyon.; Francia
Fil: De Felice, Fernanda G.. Universidade Federal do Rio de Janeiro; Brasil
Fil: 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
Fil: Ferreira, Sergio Teixeira. Universidade Federal do Rio de Janeiro; Brasil
description Soluble 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.
publishDate 2010
dc.date.none.fl_str_mv 2010-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/193100
Decker, 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
0022-3042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/193100
identifier_str_mv Decker, 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
0022-3042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/ 10.1111/j.1471-4159.2010.07058.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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