title: Ca2+-permeable AMPA receptor: A new perspective on amyloid-beta mediated pathophysiology of Alzheimer's disease.
abstract: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the primary conduits of excitatory synaptic transmission. AMPARs are predominantly Ca2+-impermeable in the matured excitatory synapse, except under certain circumstances. Growing evidence implicates the Ca2+permeability of AMPARs in the regulation of long-term synaptic plasticity and in the pathophysiology of several neurological disorders. Therefore, the Ca2+conductance of AMPARs may have both physiological and pathological roles at synapses. However, our understanding of the role of Ca2+permeable AMPARs (CP-AMPARs) in Alzheimer's disease is limited. Here we discuss insights into the potential CP-AMPAR mediated pathophysiology of Alzheimer's disease, including: 1. Ca2+-mediated aberrant regulation of synapse weakening mechanisms, and 2. neuronal network dysfunction in the brain. Consideration of CP-AMPARs as primary drivers of pathophysiology could help in understanding synaptopathologies, and highlights the potential of CP-AMPARs as therapeutic targets in Alzheimer's disease. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.
authors: Garry
authors: G
authors: Whitehead
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.
authors: Philip
authors: P
authors: Regan
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK; Centre for Synaptic Plasticity, Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.
authors: Daniel J
authors: DJ
authors: Whitcomb
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK; Centre for Synaptic Plasticity, Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK. Electronic address: Kei.Cho@Bristol.ac.uk.
authors: Kwangwook
authors: K
authors: Cho
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D016229:Amyloid beta-Peptides; D018091:Receptors, AMPA; D002118:Calcium
keywords: Amyloid beta; Calcium permeable AMPA receptor; Glucocorticoid; Hippocampus; Synaptic plasticity