Fig. 2.

RAR and RXR ligands affect Aβ42 aggregation to different extents. (A) Kinetic profiles of the aggregation of a 2 μM solution of Aβ42 in the absence and presence of 3 M eq of RAR and RXR ligands, shown in different colors. Note that Aβ42 did not aggregate within 10 h in the presence of five of the 13 molecules, seen as flat lines. (B) Kinetic profiles of 2 μM Aβ42 aggregation in the absence and presence of substoichoimetric ratios of the five molecules that are shown as flat lines in A. (C and D) Comparative time course of the formation of 2 μM Aβ42 fibrils in the absence and presence of 3 M eq of the small molecules using a dot-blot assay. Aβ42 in (D, Top) did not aggregate in the presence of 3 M eq of adapalene, MM11253, BMS493, CD1530, and LE135; therefore, the aggregation kinetics of 2 μM Aβ42 were repeated in the presence of substoichiometric quantities of the same molecules (0.5 M eq) (D, Bottom). The plots show, as histograms, the half-times of the aggregation reactions of Aβ42 from A and B and, as open circles, the correlation between the normalized dot-blot intensities with respect to the correlation in the presence of 1% DMSO at 1.6 h and 2 h (E) and 1.5 h and 2.5 h (F) of the aggregation reactions from C and D. The molecules were separated into two sets according to their potency, which was evaluated based on the extent of the delay that they induced in Aβ42 aggregation. (E) Set A (highlighted in light green) contains the molecules showing an effect similar to or greater than that of bexarotene (the half-time of Aβ42 aggregation in the absence and presence of bexarotene are highlighted with dotted black and red lines, respectively). AU, arbitrary units. (F) Molecules classified as set B (highlighted in light orange) inhibited the aggregation of Aβ42 completely within 10 h in the presence of 3 M eq of the small molecules.