Web of Science: 51 citas, Scopus: 53 citas, Google Scholar: citas
Soluble oligomers of amyloid-beta peptide disrupt membrane trafficking of alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid receptor (AMPAR) contributing to early synapse dysfunction
Miñano Molina, Alfredo Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
España Agustí, Judit (Universitat Autònoma de Barcelona. Institut de Neurociències)
Martín, Elsa (Universitat Autònoma de Barcelona. Institut de Neurociències)
Barneda Zahonero, Bruna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Fadó Andrés, Rut (Universitat Autònoma de Barcelona. Institut de Neurociències)
Solé Piñol, Montserrat (Universitat Autònoma de Barcelona. Institut de Neurociències)
Trullas i Oliva, Ramon (Centro de Investigación Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED))
Saura Antolín, Carlos A. (Carlos Alberto) (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Rodríguez Álvarez, José (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)

Fecha: 2011
Resumen: β-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie the pathophysiology of Alzheimer disease (AD). Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading to cognitive failure associated with AD. The Aβ-induced synaptic dysfunction has been attributed to the synaptic removal of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs). However, the molecular mechanisms underlying the loss of AMPAR induced by Aβ at synapses are largely unknown. In this study we have examined the effect of Aβ oligomers on phosphorylated GluA1 at serine 845, a residue that plays an essential role in the trafficking of AMPARs toward extrasynaptic sites and the subsequent delivery to synapses during synaptic plasticity events. We found that Aβ oligomers reduce basal levels of Ser-845 phosphorylation and surface expression of AMPARs affecting AMPAR subunit composition. Aβ-induced GluA1 dephosphorylation and reduced receptor surface levels are mediated by an increase in calcium influx into neurons through ionotropic glutamate receptors and activation of the calcium-dependent phosphatase calcineurin. Moreover, Aβ oligomers block the extrasynaptic delivery of AMPARs induced by chemical synaptic potentiation. In addition, reduced levels of total and phosphorylated GluA1 are associated with initial spatial memory deficits in a transgenic mouse model of AD. These findings indicate that Aβ oligomers could act as a synaptic depressor affecting the mechanisms involved in the targeting of AMPARs to the synapses during early stages of the disease.
Nota: Número d'acord de subvenció MICINN/SAF2008-01904
Nota: Número d'acord de subvenció MICINN/SAF2010-20925
Nota: Número d'acord de subvenció ISCIII/RD06/0026/1009
Nota: Número d'acord de subvenció CIBERNED/CB06/05/0042
Derechos: Tots els drets reservats.
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Materia: Alzheimer Disease ; Amyloid ; Calcineurin ; Calcium ; Glutamate Receptors Ionotropic (AMPA and NMDA) ; GluR1 ; Phosphorylation
Publicado en: The Journal of biological chemistry, Vol. 286, No. 31 (2011) , p. 543-557, ISSN 1083-351X

DOI: 10.1074/jbc.M111.227504


11 p, 1.9 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
Artículos > Artículos de investigación
Artículos > Artículos publicados

 Registro creado el 2017-03-21, última modificación el 2019-05-23



   Favorit i Compartir