Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
Irene Álvarez-Berbel,
Alba Espargaró,
Antonio Viayna,
Ana Belén Caballero,
Maria Antònia Busquets,
Patrick Gámez,
Francisco Javier Luque,
Raimon Sabaté
Affiliations
Irene Álvarez-Berbel
Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
Alba Espargaró
Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
Antonio Viayna
Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy, Institute of Theoretical and Computational Chemistry (IQTCUB) and Institute of Biomedicine (IBUB), Campus Torribera, University of Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain
Ana Belén Caballero
Department of Inorganic and Organic Chemistry, Faculty of Chemistry, Institute of Nanoscience and Nanotechnology (IN2UB) and NanoBIC, University of Barcelona, 08028 Barcelona, Spain
Maria Antònia Busquets
Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
Patrick Gámez
Department of Inorganic and Organic Chemistry, Faculty of Chemistry, Institute of Nanoscience and Nanotechnology (IN2UB) and NanoBIC, University of Barcelona, 08028 Barcelona, Spain
Francisco Javier Luque
Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy, Institute of Theoretical and Computational Chemistry (IQTCUB) and Institute of Biomedicine (IBUB), Campus Torribera, University of Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain
Raimon Sabaté
Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
One of the pathological hallmarks of Alzheimer’s disease (AD) is the formation of amyloid-β plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-β 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 Aβ40 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 Aβ40 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.
