NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes

N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors with key roles in synaptic communication and plasticity. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs can promote cell death underlying a potent...

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Detalles Bibliográficos
Autores: Escamilla, Sergio, Sáez-Valero, Javier, Cuchillo-Ibáñez, Inmaculada
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/380371
Acceso en línea:http://hdl.handle.net/10261/380371
https://api.elsevier.com/content/abstract/scopus_id/85205248526
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
GluN1
GluN2A
GluN2B
NMDAR
Excitotoxicity
Extrasynaptic NMDAR
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spelling NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic MembranesEscamilla, SergioSáez-Valero, JavierCuchillo-Ibáñez, InmaculadaAlzheimer’s diseaseGluN1GluN2AGluN2BNMDARExcitotoxicityExtrasynaptic NMDARN-methyl-D-aspartate receptors (NMDARs) are glutamate receptors with key roles in synaptic communication and plasticity. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs can promote cell death underlying a potential mechanism of neurodegeneration occurring in Alzheimer's disease (AD). The distribution of synaptic versus extrasynaptic NMDARs has emerged as an important parameter contributing to neuronal dysfunction in neurodegenerative diseases including AD. Here, we review the concept of extrasynaptic NMDARs, as this population is present in numerous neuronal cell membranes but also in the membranes of various non-neuronal cells. Previous evidence regarding the membranal distribution of synaptic versus extrasynaptic NMDRs in relation to AD mice models and in the brains of AD patients will also be reviewed.This research was funded by Fondo de Investigaciones Sanitarias (PI22-01329, co-funded by the Fondo Europeo de Desarrollo Regional, FEDER “Investing in your future”), CIBERNED (Instituto de Salud Carlos III, Spain), ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante), and the Direcció General de Ciència i Investigació, Generalitat Valenciana (AICO/2021/308). We acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (CEX2021-001165-S). Sergio Escamilla is funded by the Instituto Carlos III de Madrid (PFIS fellowship).With funding from the Spanish government through the "Severo Ochoa Centre of Excelence" accreditation (CEX2021-001165-S)Peer reviewedMultidisciplinary Digital Publishing InstituteEuropean CommissionInstituto de Salud Carlos IIIInstituto de Investigación Sanitaria y Biomédica de AlicanteGeneralitat ValencianaMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Sáez-Valero, Javier [0000-0001-7480-320X]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/380371https://api.elsevier.com/content/abstract/scopus_id/85205248526reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII//PI22-01329info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001165-Shttps://doi.org/10.3390/ijms251810220Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3803712026-05-22T06:33:51Z
dc.title.none.fl_str_mv NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
title NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
spellingShingle NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
Escamilla, Sergio
Alzheimer’s disease
GluN1
GluN2A
GluN2B
NMDAR
Excitotoxicity
Extrasynaptic NMDAR
title_short NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
title_full NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
title_fullStr NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
title_full_unstemmed NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
title_sort NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes
dc.creator.none.fl_str_mv Escamilla, Sergio
Sáez-Valero, Javier
Cuchillo-Ibáñez, Inmaculada
author Escamilla, Sergio
author_facet Escamilla, Sergio
Sáez-Valero, Javier
Cuchillo-Ibáñez, Inmaculada
author_role author
author2 Sáez-Valero, Javier
Cuchillo-Ibáñez, Inmaculada
author2_role author
author
dc.contributor.none.fl_str_mv European Commission
Instituto de Salud Carlos III
Instituto de Investigación Sanitaria y Biomédica de Alicante
Generalitat Valenciana
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Sáez-Valero, Javier [0000-0001-7480-320X]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Alzheimer’s disease
GluN1
GluN2A
GluN2B
NMDAR
Excitotoxicity
Extrasynaptic NMDAR
topic Alzheimer’s disease
GluN1
GluN2A
GluN2B
NMDAR
Excitotoxicity
Extrasynaptic NMDAR
description N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors with key roles in synaptic communication and plasticity. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs can promote cell death underlying a potential mechanism of neurodegeneration occurring in Alzheimer's disease (AD). The distribution of synaptic versus extrasynaptic NMDARs has emerged as an important parameter contributing to neuronal dysfunction in neurodegenerative diseases including AD. Here, we review the concept of extrasynaptic NMDARs, as this population is present in numerous neuronal cell membranes but also in the membranes of various non-neuronal cells. Previous evidence regarding the membranal distribution of synaptic versus extrasynaptic NMDRs in relation to AD mice models and in the brains of AD patients will also be reviewed.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/380371
https://api.elsevier.com/content/abstract/scopus_id/85205248526
url http://hdl.handle.net/10261/380371
https://api.elsevier.com/content/abstract/scopus_id/85205248526
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII//PI22-01329
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001165-S
https://doi.org/10.3390/ijms251810220
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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