Figure 6.

Schematic depiction of possible effects of potential anti-amyloid compounds on the amyloid aggregation reaction performed under distinct environmental conditions. Different environmental conditions can lead to the formation of distinct aggregate species of which only some are targeted by the compound (A), as in case of insulin aggregation in PB-Q and AC-Q. Certain compounds can also interfere with ThT’s fluorescence intensity (B), suggesting inhibition, which was not confirmed by other experiments, such as the quantification of soluble protein at the final plateau of ThT intensity. An example is EGCG and $\alpha$-synuclein at pH 6. Moreover, specific environmental conditions can induce modifications of the compound, which results in the generation of products that target aggregation prone species (C), as in the case of $\alpha$-synuclein aggregation at neutral pH. The compound modification can only manifest itself if it occurs with kinetics comparable to, or faster than the kinetics of aggregation. Distinct background colours represent different environmental conditions. Different shapes of aggregates represent distinct pathways reflecting the observed polymorphism of amyloid fibrils.