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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 (Aâ) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism by which Aâ exerts its neurotoxic effect is largely unknown. It has been suggested that the peptide can bind to the á7 nicotinic acetylcholine receptor (á7nAChR). In this study, we examined the binding of Aâ1-42 to endogenous and recombinantly expressed á7nAChRs. Aâ1-42 did neither inhibit the specific binding of á7nAChR ligands to rat brain homogenate or slice preparations, nor did it influence the activity of á7nAChRs expressed in Xenopus oocytes. Similarly, Aâ1-42 did not compete for á-bungarotoxin-binding sites on SH-SY5Y cells stably expressing á7nAChRs. The effect of the Aâ1-42 on tau phosphorylation was also examined. Although Aâ1-42 altered tau phosphorylation in á7nAChR-transfected SH-SY5Y cells, the effect of the peptide was unrelated to á7nAChR expression or activity. Binding studies using surface plasmon resonance indicated that the majority of the Aâ bound to membrane lipid, rather than to a protein component. Fluorescence anisotropy experiments indicated that Aâ may disrupt membrane lipid structure or fluidity. We conclude that the effects of Aâ are unlikely to be mediated by direct binding to the á7nAChR. Instead, we speculate that Aâ 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: | 80 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2010-02-25 |
| Last Modified: | 2010-09-16 |
| Downloads: | 0 |
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