Fig. 1
Trodusquemine enhances the overall rate of Aβ42 aggregation by promoting secondary nucleation. a Structure of trodusquemine (TRO). Kinetic profiles of the aggregation of 2 µM Aβ42 in the absence (black) or presence of trodusquemine at ratios of Aβ42-to-trodusquemine of 10:1, 5:1 and 1:1 (light to dark blue) in the absence of seeds (b), in the presence of 5% seeds (c) and in the presence of 25% seeds (d). Solid lines indicate theoretical predictions based on kinetic fitting (see Results); the data are very well-described by varying the rates associated with the presence of trodusquemine in the secondary pathway (k+k2) (b), or associated with monomer-dependent secondary nucleation (k2) (c). e Change of the half-time of aggregation of Aβ42 as seen from b to d. f Dependency of the apparent reaction rate constants of secondary pathways (k+k2app) on increasing concentrations of trodusquemine relative to the condition in the absence of the molecule (k+k2). The schematic depicts the microscopic steps involved in Aβ42 aggregation. In all panels, error bars indicate standard error of the mean (s.e.m.) of three replicates
