Interaction of tacrine and velnacrine with neocortical synaptosomal membranes: relevance to Alzheimer's disease |
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Authors: | DA Butterfield K Hensley N Hall S Umhauer J Carney |
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Affiliation: | Department of Chemistry, University of Kentucky, Lexington 40506-0055. |
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Abstract: | The acridine-based, potential Alzheimer's disease therapeutic agents, tacrine and velnacrine, were incubated with rat or gerbil neocortical synaptosomal membranes. Electron paramagnetic resonance employing a protein-specific spin label was used to monitor this interaction. Analogous to their effects in erythrocyte membranes [Butterfield and Rangachari (1992) Biochem. Biophys. Res. Commun. 185: 596-603], in the present studies both agents decreased segmental motion of spin labeled synaptosomal membrane proteins, consistent with increased cytoskeletal protein-protein interactions (0.001 < P < 0.005), and tacrine was more potent than velnacrine. These results are discussed with possible relevance to molecular actions of the agents and molecular alterations in Alzheimer's disease. |
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