Small molecules inhibit fibril formation.
a, ThT assays showed that several compounds isolated in the HTS inhibited the fibrillization of Aβ42. *, p < 0.05 relative to the control: D737, p = 0.001; D594, p = 0.008; and D621, p = 0.021. (Two compounds, D281 and D514, produced large increases in ThT fluorescence, suggesting that these compounds either stimulate fibrillogenesis or cause fibrils to assume altered conformations with enhanced ThT binding and/or fluorescence.) b, time course of inhibition of Aβ42 fibrillization by D737. Black line, 20 μm Aβ42 without D737; gray line, 20 μm Aβ42 with 50 μm D737. c, transmission EM of Aβ42 fibril formation in the absence or presence of 50 μm D737. d, dose-dependent inhibition of Aβ42 fibrillization by compound D737. a.u., absorbance units.