Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction

One of the pathological hallmarks of Alzheimer's disease (AD) is the formation of amyloid-beta plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-beta aggregation, hence being complementary to the palliative treatment of cholinergic decline. Antiaggregation assays performed for apigenin and quercetin, which are polyphenolic compounds that exhibit inhibitory properties against the formation of amyloid plaques, reveal distinct inhibitory effects of these compounds on A beta 40 aggregation in the presence and absence of AChE. Furthermore, the analysis of the amyloid fibers formed in the presence of these flavonoids suggests that the A beta 40 aggregates present different quaternary structures, viz., smaller molecular assemblies are generated. In agreement with a noncompetitive inhibition of AChE, molecular modeling studies indicate that these effects may be due to the binding of apigenin and quercetin at the peripheral binding site of AChE. Since apigenin and quercetin can also reduce the generation of reactive oxygen species, the data achieved suggest that multitarget catechol-type compounds may be used for the simultaneous treatment of various biological hallmarks of AD.

Automated summary

One of the pathological features of Alzheimer's disease is the formation of amyloid-beta plaques. Inhibiting the enzyme acetylcholinesterase can slow down this process, and compounds like apigenin and quercetin also have inhibitory effects on plaque formation. These compounds can also affect the structure of amyloid fibers. Molecular modeling studies suggest that these effects may be due to the binding of apigenin and quercetin to acetylcholinesterase. Additionally, these compounds can reduce the production of reactive oxygen species, suggesting their potential use in targeting multiple biological features of Alzheimer's disease.