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

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• 作者：Garry Whitehead^a ; Philip Regan^a ; Daniel J. Whitcomb^a ; ^b ; Kwangwook Cho^a ; ^b ; ^{Kei.Cho@Bristol.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Calcium permeable AMPA receptor ; Amyloid beta ; Glucocorticoid ; Synaptic plasticity ; Hippocampus
• 刊名：Neuropharmacology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：112
• 期：part_PA
• 页码：221-227
• 全文大小：709 K

文摘

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’.