amyloid-beta-peptides and tranilast

The antiallergy and potential anticancer drug tranilast has been patented for treating Alzheimer's disease (AD), in which amyloid β-protein (Aβ) plays a key pathogenic role. We used solution NMR to determine that tranilast binds to Aβ40 monomers with ∼300 μM affinity. Remarkably, tranilast increases Aβ40 fibrillation more than 20-fold in the thioflavin T assay at a 1:1 molar ratio, as well as significantly reducing the lag time. Tranilast likely promotes fibrillation by shifting Aβ monomer conformations to those capable of seed formation and fibril elongation. Molecular docking results qualitatively agree with NMR chemical shift perturbation, which together indicate that hydrophobic interactions are the major driving force of the Aβ-tranilast interaction. These data suggest that AD may be a potential complication for tranilast usage in elderly patients.

Topics: Amyloid; Amyloid beta-Peptides; Anti-Allergic Agents; Antineoplastic Agents; Benzothiazoles; Binding Sites; Fluorescent Dyes; Humans; Microscopy, Atomic Force; Molecular Docking Simulation; Nuclear Magnetic Resonance, Biomolecular; ortho-Aminobenzoates; Peptide Fragments; Protein Binding; Protein Multimerization; Protein Structure, Quaternary; Thiazoles