Ca2+-permeable AMPA receptor: A new perspective on amyloid-beta mediated pathophysiology of Alzheimer's disease

NEUROPHARMACOLOGY

卷:112

Review

Whitehead, Garry¹  Regan, Philip¹  Whitcomb, Daniel J.^1,2  Cho, Kwangwook^1,2 

[1] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Fac Hlth Sci, Whitson St, Bristol BS1 3NY, Avon, England

[2] Univ Bristol, Ctr Synapt Plast, Fac Hlth Sci, Whitson St, Bristol BS1 3NY, Avon, England

关键词: Calcium permeable AMPA receptor;    Amyloid beta;    Glucocorticoid;    Synaptic plasticity;    Hippocampus;   

DOI  :  10.1016/j.neuropharm.2016.08.022

来源: Elsevier

【 摘 要 】

alpha-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 understandirig 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: I. 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 'lonotropic glutamate receptors'. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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