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Neuronal receptors as targets for the action of amyloid-beta protein (Aβ) in the brain

Published online by Cambridge University Press:  20 January 2012

Aarti N. Patel  and
Jack H. Jhamandas
Aarti N. Patel
Affiliation:
Division of Neurology, Department of Medicine, Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Jack H. Jhamandas*
Affiliation:
Division of Neurology, Department of Medicine, Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
*
*Corresponding author: Jack H. Jhamandas, Department of Medicine (Neurology), University of Alberta, 530 Heritage Medical Research Centre, Edmonton, Alberta, Canada T6 G 2S2. E-mail: jack.jhamandas@ualberta.ca
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Abstract

Accumulation of neurotoxic soluble amyloid-beta protein (Aβ) oligomers in the brains of patients with Alzheimer disease (AD) and their role in AD pathogenesis have emerged as topics of considerable interest in recent years. Soluble Aβ oligomers impair synaptic and neuronal function, leading to neurodegeneration that is clinically manifested by memory and cognitive dysfunction. The precise mechanisms whereby Aβ oligomers cause neurotoxicity remain unknown. Emerging insights into the mechanistic link between neuronal receptors and soluble Aβ oligomers highlight the potential role of these receptors in Aβ-mediated neurotoxicity in AD. The current review focuses on studies describing interactions between soluble Aβ oligomers and neuronal receptors, and their role in AD pathogenesis. Furthermore, these studies provide insight into potential therapies for AD using compounds directed at putative target receptors for the action of Aβ in the central nervous system. We focus on interactions of Aβ with subtypes of acetylcholine and glutamatergic receptors. Additionally, neuronal receptors such as insulin, amylin and receptor for advanced glycation end products could be potential targets for soluble Aβ-oligomer-mediated neurotoxicity. Aβ interactions with other receptors such as the p75 neurotrophin receptors, which are highly expressed on cholinergic basal forebrain neurons lost in AD, are also highlighted.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 14 , March 2012 , e2
Copyright
Copyright © Cambridge University Press 2012

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References

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Further reading

The reader is referred to Refs 27, 32, 33, 35, 40 and 73 for reviews on Aβ protein and synaptic function, and amyloid interactions with specific types of neuronal receptors.