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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9699245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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