Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
Escamilla, Sergio (Universidad Miguel Hernández de Elche)
Badillos Rodríguez, Raquel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Comella i Carnicé, Joan Xavier 1963- (Universitat Autònoma de Barcelona. Institut de Neurociències)
Solé Piñol, Montserrat (Universitat Autònoma de Barcelona. Institut de Neurociències)
Pérez-Otaño, Isabel (Universidad Miguel Hernández de Elche)
Mut, Jose V. Sánchez (Universidad Miguel Hernández de Elche)
Sáez-Valero, Javier (Universidad Miguel Hernández de Elche)
Cuchillo-Ibáñez, Inmaculada (Universidad Miguel Hernández de Elche)

Date:	2024
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI22/01329
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; Extrasynaptic ; GluN1 ; GluN2A ; GluN2B ; GluN3A ; Human ; NMDA ; Tyr1336 ; Tyr1472
Published in:	Alzheimer's & dementia, Vol. 20 (october 2024) , p. 8231-8245, ISSN 1552-5279

DOI: 10.1002/alz.14125
PMID: 39450669

15 p, 3.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles