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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-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 pall...

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Autores principales: Álvarez-Berbel, Irene, Espargaró, Alba, Viayna, Antonio, Caballero, Ana Belén, Busquets, Maria Antònia, Gámez, Patrick, Luque, Francisco Javier, Sabaté, Raimon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699245/
https://www.ncbi.nlm.nih.gov/pubmed/36365159
http://dx.doi.org/10.3390/pharmaceutics14112342
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author Álvarez-Berbel, Irene
Espargaró, Alba
Viayna, Antonio
Caballero, Ana Belén
Busquets, Maria Antònia
Gámez, Patrick
Luque, Francisco Javier
Sabaté, Raimon
author_facet Álvarez-Berbel, Irene
Espargaró, Alba
Viayna, Antonio
Caballero, Ana Belén
Busquets, Maria Antònia
Gámez, Patrick
Luque, Francisco Javier
Sabaté, Raimon
author_sort Álvarez-Berbel, Irene
collection PubMed
description 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.
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spelling pubmed-96992452022-11-26 Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction Álvarez-Berbel, Irene Espargaró, Alba Viayna, Antonio Caballero, Ana Belén Busquets, Maria Antònia Gámez, Patrick Luque, Francisco Javier Sabaté, Raimon Pharmaceutics Article 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. MDPI 2022-10-30 /pmc/articles/PMC9699245/ /pubmed/36365159 http://dx.doi.org/10.3390/pharmaceutics14112342 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Álvarez-Berbel, Irene
Espargaró, Alba
Viayna, Antonio
Caballero, Ana Belén
Busquets, Maria Antònia
Gámez, Patrick
Luque, Francisco Javier
Sabaté, Raimon
Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
title Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
title_full Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
title_fullStr Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
title_full_unstemmed Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
title_short Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
title_sort three to tango: inhibitory effect of quercetin and apigenin on acetylcholinesterase, amyloid-β aggregation and acetylcholinesterase-amyloid interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699245/
https://www.ncbi.nlm.nih.gov/pubmed/36365159
http://dx.doi.org/10.3390/pharmaceutics14112342
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