The beta-amyloid protein of Alzheimer's disease does not bind to the alpha7 nicotinic acetylcholine receptor

SMALL, D, Maksel, D, Kerr, M, Ng, J, Hou, X, Chu, C, Mehrani, H, Unabia, S, Azari, M, Loiacono, R, Aguilar, M and Chebib, M 2007, 'The beta-amyloid protein of Alzheimer's disease does not bind to the alpha7 nicotinic acetylcholine receptor', Journal of Neurochemistry, vol. 101, no. 6, pp. 1527-1538.


Document type: Journal Article
Collection: Journal Articles

Title The beta-amyloid protein of Alzheimer's disease does not bind to the alpha7 nicotinic acetylcholine receptor
Author(s) SMALL, D
Maksel, D
Kerr, M
Ng, J
Hou, X
Chu, C
Mehrani, H
Unabia, S
Azari, M
Loiacono, R
Aguilar, M
Chebib, M
Year 2007
Journal name Journal of Neurochemistry
Volume number 101
Issue number 6
Start page 1527
End page 1538
Total pages 12
Publisher Wiley-Blackwell Publishing Ltd
Abstract Accumulation of the amyloid protein (Aß) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism by which Aß exerts its neurotoxic effect is largely unknown. It has been suggested that the peptide can bind to the a7 nicotinic acetylcholine receptor (a7nAChR). In this study, we examined the binding of Aß1-42 to endogenous and recombinantly expressed a7nAChRs. Aß1-42 did neither inhibit the specific binding of a7nAChR ligands to rat brain homogenate or slice preparations, nor did it influence the activity of a7nAChRs expressed in Xenopus oocytes. Similarly, Aß1-42 did not compete for a-bungarotoxin-binding sites on SH-SY5Y cells stably expressing a7nAChRs. The effect of the Aß1-42 on tau phosphorylation was also examined. Although Aß1-42 altered tau phosphorylation in a7nAChR-transfected SH-SY5Y cells, the effect of the peptide was unrelated to a7nAChR expression or activity. Binding studies using surface plasmon resonance indicated that the majority of the Aß bound to membrane lipid, rather than to a protein component. Fluorescence anisotropy experiments indicated that Aß may disrupt membrane lipid structure or fluidity. We conclude that the effects of Aß are unlikely to be mediated by direct binding to the a7nAChR. Instead, we speculate that Aß may exert its effects by altering the packing of lipids within the plasma membrane, which could, in turn, influence the function of a variety of receptors and channels on the cell surface. © 2007 The Authors
Subject Cellular Nervous System
Keyword(s) Amyloid
Cholinergic
Dementia
Nicotinic
Toxicity
DOI - identifier 10.1111/j.1471-4159.2006.04444.x
Copyright notice © 2007 International Society for Neurochemistry
ISSN 0022-3042
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