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The β-amyloid protein of Alzheimer's disease binds to membrane lipids but does not bind to the α7 nicotinic acetylcholine receptor

Citation

Small, DH and Maksel, D and Kerr, ML and Ng, J and Hou, X and Chu, C and Mehrani, H and Unabia, S and Azari, MF and Loiacono, R and Aguilar, MI and Chebib, M, The β-amyloid protein of Alzheimer's disease binds to membrane lipids but does not bind to the α7 nicotinic acetylcholine receptor, Journal of Neurochemistry, 101, (6) pp. 1527-1538. ISSN 0022-3042 (2007) [Refereed Article]

DOI: doi:10.1111/j.1471-4159.2006.04444.x

Abstract

Accumulation of the amyloid protein (A) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism by which A exerts its neurotoxic effect is largely unknown. It has been suggested that the peptide can bind to the 7 nicotinic acetylcholine receptor (7nAChR). In this study, we examined the binding of A1-42 to endogenous and recombinantly expressed 7nAChRs. A1-42 did neither inhibit the specific binding of 7nAChR ligands to rat brain homogenate or slice preparations, nor did it influence the activity of 7nAChRs expressed in Xenopus oocytes. Similarly, A1-42 did not compete for -bungarotoxin-binding sites on SH-SY5Y cells stably expressing 7nAChRs. The effect of the A1-42 on tau phosphorylation was also examined. Although A1-42 altered tau phosphorylation in 7nAChR-transfected SH-SY5Y cells, the effect of the peptide was unrelated to 7nAChR expression or activity. Binding studies using surface plasmon resonance indicated that the majority of the A bound to membrane lipid, rather than to a protein component. Fluorescence anisotropy experiments indicated that A may disrupt membrane lipid structure or fluidity. We conclude that the effects of A are unlikely to be mediated by direct binding to the 7nAChR. Instead, we speculate that A 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:61099
Year Published:2007
Web of Science® Times Cited:79
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-02-25
Last Modified:2010-09-16
Downloads:0

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