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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/193100
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:33:40Zoai: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:34982025-09-29 09:33:40.979CONICET 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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1844613036715802624 |
score |
13.070432 |