Ca2+-permeable AMPA receptor

A new perspective on amyloid-beta mediated pathophysiology of Alzheimer's disease

Garry Whitehead, Philip Regan, Daniel J Whitcomb, Kwangwook Cho

Research output: Contribution to journalReview article

14 Citations (Scopus)

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'.

Original languageEnglish
Pages (from-to)221-227
Number of pages7
JournalNeuropharmacology
Volume112
Issue numberPt A
Early online date22 Aug 2016
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Alzheimer Disease/metabolism
  • Amyloid beta-Peptides/administration & dosage
  • Animals
  • Calcium/metabolism
  • Hippocampus/metabolism
  • Humans
  • Neuronal Plasticity
  • Neurons/metabolism
  • Receptors, AMPA/metabolism
  • Synapses/metabolism
  • Synaptic Transmission

Cite this

Ca2+-permeable AMPA receptor : A new perspective on amyloid-beta mediated pathophysiology of Alzheimer's disease. / Whitehead, Garry; Regan, Philip; Whitcomb, Daniel J; Cho, Kwangwook.

In: Neuropharmacology, Vol. 112, No. Pt A, 01.01.2017, p. 221-227.

Research output: Contribution to journalReview article

Whitehead, Garry ; Regan, Philip ; Whitcomb, Daniel J ; Cho, Kwangwook. / Ca2+-permeable AMPA receptor : A new perspective on amyloid-beta mediated pathophysiology of Alzheimer's disease. In: Neuropharmacology. 2017 ; Vol. 112, No. Pt A. pp. 221-227.
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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'.",
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