Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Multiple ligand binding sites on A beta(1-40) fibrils.

LeVine H

Department of Molecular and Cellular Biochemistry, Chandler School of Medicine and the Center on Aging, University of Kentucky, USA. hlevine@email.uky.edu

Although the structures of Thioflavin T and another benzothiazole, BTA-1, are similar, they bind to A beta non-competitively, probably to different sites on the A beta(1-40) fibrils. The amyloid fibril-induced fluorescence of ThT that corresponds to a fraction of total ThT binding is not displaced by high concentrations of (S)-naproxen or (R)-ibuprofen, which are reported to potently block high affinity binding of the radiolabeled malononitrile FDDNP and derivatives. The binding of the benzothiazole ligands is significantly substoichiometric with respect to A beta(1-40) monomer peptide, unlike Congo Red, which binds to A beta(1-40) fibrils on a 1:1 basis with monomer peptide. These results indicate that there are multiple domains for ligand binding to amyloid fibrils and suggest that it may be possible to design ligands that bind selectively to particular forms of fibrils that are connected with the pathogenesis of Alzheimer's disease and potentially other protein misfolding diseases.

Published 3 August 2005 in Amyloid, 12(1): 5-14.
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