Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients

Synaptic and extrasynaptic distribution of N-methyl-D-aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer's disease (AD) subjects, despite their contribution to neurodegeneration. We have developed a protocol to isolate synaptic and extrasynaptic membranes from contr...

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Autores: Escamilla, Sergio, Badillos Rodríguez, Raquel|||0000-0002-8257-1784, Comella i Carnicé, Joan Xavier|||0000-0002-6218-0786, Solé Piñol, Montserrat|||0000-0003-4240-6562, Pérez-Otaño, Isabel, Sánchez-Mut, José Vicente|||0000-0002-9292-8521, Sáez-Valero, Javier, Cuchillo-Ibáñez, Inmaculada|||0000-0002-3689-5518
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:305693
Acceso en línea:https://ddd.uab.cat/record/305693
https://dx.doi.org/urn:doi:10.1002/alz.14125
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
Extrasynaptic
GluN1
GluN2A
GluN2B
GluN3A
Human
NMDA
Tyr1336
Tyr1472
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spelling Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patientsEscamilla, SergioBadillos Rodríguez, Raquel|||0000-0002-8257-1784Comella i Carnicé, Joan Xavier|||0000-0002-6218-0786Solé Piñol, Montserrat|||0000-0003-4240-6562Pérez-Otaño, IsabelSánchez-Mut, José Vicente|||0000-0002-9292-8521Sáez-Valero, JavierCuchillo-Ibáñez, Inmaculada|||0000-0002-3689-5518Alzheimer's diseaseExtrasynapticGluN1GluN2AGluN2BGluN3AHumanNMDATyr1336Tyr1472Synaptic and extrasynaptic distribution of N-methyl-D-aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer's disease (AD) subjects, despite their contribution to neurodegeneration. We have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B, GluN2A, GluN1, and GluN3A, as well as post-translational modifications, such as phosphorylation and glycosylation. Lower levels of synaptic GluN2B and GluN2A were found in AD fractions, while extrasynaptic GluN2B and GluN1 levels were significantly higher; GluN3A distribution remained unaffected in AD. We also identified different glycoforms of GluN2B and GluN2A in extrasynaptic membranes. Synaptic Tyr1472 GluN2B phosphorylation was significantly lower in AD fractions. Reduction of synaptic NMDAR subunits, particularly for GluN2B, is likely to contribute to synaptic transmission failure in AD. Additionally, the increment of extrasynaptic NMDAR subunits could favor the activation of excitotoxicity in AD. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/305693https://dx.doi.org/urn:doi:10.1002/alz.14125reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22/01329open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3056932026-06-06T12:50:31Z
dc.title.none.fl_str_mv Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
title Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
spellingShingle Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
Escamilla, Sergio
Alzheimer's disease
Extrasynaptic
GluN1
GluN2A
GluN2B
GluN3A
Human
NMDA
Tyr1336
Tyr1472
title_short Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
title_full Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
title_fullStr Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
title_full_unstemmed Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
title_sort Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
dc.creator.none.fl_str_mv Escamilla, Sergio
Badillos Rodríguez, Raquel|||0000-0002-8257-1784
Comella i Carnicé, Joan Xavier|||0000-0002-6218-0786
Solé Piñol, Montserrat|||0000-0003-4240-6562
Pérez-Otaño, Isabel
Sánchez-Mut, José Vicente|||0000-0002-9292-8521
Sáez-Valero, Javier
Cuchillo-Ibáñez, Inmaculada|||0000-0002-3689-5518
author Escamilla, Sergio
author_facet Escamilla, Sergio
Badillos Rodríguez, Raquel|||0000-0002-8257-1784
Comella i Carnicé, Joan Xavier|||0000-0002-6218-0786
Solé Piñol, Montserrat|||0000-0003-4240-6562
Pérez-Otaño, Isabel
Sánchez-Mut, José Vicente|||0000-0002-9292-8521
Sáez-Valero, Javier
Cuchillo-Ibáñez, Inmaculada|||0000-0002-3689-5518
author_role author
author2 Badillos Rodríguez, Raquel|||0000-0002-8257-1784
Comella i Carnicé, Joan Xavier|||0000-0002-6218-0786
Solé Piñol, Montserrat|||0000-0003-4240-6562
Pérez-Otaño, Isabel
Sánchez-Mut, José Vicente|||0000-0002-9292-8521
Sáez-Valero, Javier
Cuchillo-Ibáñez, Inmaculada|||0000-0002-3689-5518
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease
Extrasynaptic
GluN1
GluN2A
GluN2B
GluN3A
Human
NMDA
Tyr1336
Tyr1472
topic Alzheimer's disease
Extrasynaptic
GluN1
GluN2A
GluN2B
GluN3A
Human
NMDA
Tyr1336
Tyr1472
description Synaptic and extrasynaptic distribution of N-methyl-D-aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer's disease (AD) subjects, despite their contribution to neurodegeneration. We have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B, GluN2A, GluN1, and GluN3A, as well as post-translational modifications, such as phosphorylation and glycosylation. Lower levels of synaptic GluN2B and GluN2A were found in AD fractions, while extrasynaptic GluN2B and GluN1 levels were significantly higher; GluN3A distribution remained unaffected in AD. We also identified different glycoforms of GluN2B and GluN2A in extrasynaptic membranes. Synaptic Tyr1472 GluN2B phosphorylation was significantly lower in AD fractions. Reduction of synaptic NMDAR subunits, particularly for GluN2B, is likely to contribute to synaptic transmission failure in AD. Additionally, the increment of extrasynaptic NMDAR subunits could favor the activation of excitotoxicity in AD.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/305693
https://dx.doi.org/urn:doi:10.1002/alz.14125
url https://ddd.uab.cat/record/305693
https://dx.doi.org/urn:doi:10.1002/alz.14125
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI22/01329
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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