Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction an...

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Authors: Viayna, Elisabet, Sabaté Lagunas, Raimon, Muñoz-Torrero López-Ibarra, Diego
Format: article
Status:Versión aceptada para publicación
Publication Date:2013
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/50684
Online Access:https://hdl.handle.net/2445/50684
Access Level:Open access
Keyword:Agregació (Química)
Malaltia d'Alzheimer
Amiloïdosi
Aggregation (Chemistry)
Alzheimer's disease
Amyloidosis
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spelling Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidatesViayna, ElisabetSabaté Lagunas, RaimonMuñoz-Torrero López-Ibarra, DiegoAgregació (Química)Malaltia d'AlzheimerAmiloïdosiAggregation (Chemistry)Alzheimer's diseaseAmyloidosisNotwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.Bentham Science Publishers2014201420132014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion23 p.application/pdfhttps://hdl.handle.net/2445/50684Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://openurl.ingenta.com/content?genre=article&issn=1568-0266&volume=13&issue=15&spage=1820&epage=1842Current Topics In Medicinal Chemistry, 2013, vol. 13, num. 15, p. 1820-1842(c) Bentham Science Publishers, 2013info:eu-repo/semantics/openAccessoai:recercat.cat:2445/506842026-05-29T05:05:01Z
dc.title.none.fl_str_mv Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
title Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
spellingShingle Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
Viayna, Elisabet
Agregació (Química)
Malaltia d'Alzheimer
Amiloïdosi
Aggregation (Chemistry)
Alzheimer's disease
Amyloidosis
title_short Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
title_full Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
title_fullStr Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
title_full_unstemmed Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
title_sort Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates
dc.creator.none.fl_str_mv Viayna, Elisabet
Sabaté Lagunas, Raimon
Muñoz-Torrero López-Ibarra, Diego
author Viayna, Elisabet
author_facet Viayna, Elisabet
Sabaté Lagunas, Raimon
Muñoz-Torrero López-Ibarra, Diego
author_role author
author2 Sabaté Lagunas, Raimon
Muñoz-Torrero López-Ibarra, Diego
author2_role author
author
dc.subject.none.fl_str_mv Agregació (Química)
Malaltia d'Alzheimer
Amiloïdosi
Aggregation (Chemistry)
Alzheimer's disease
Amyloidosis
topic Agregació (Química)
Malaltia d'Alzheimer
Amiloïdosi
Aggregation (Chemistry)
Alzheimer's disease
Amyloidosis
description Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.
publishDate 2013
dc.date.none.fl_str_mv 2013
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/50684
url https://hdl.handle.net/2445/50684
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://openurl.ingenta.com/content?genre=article&issn=1568-0266&volume=13&issue=15&spage=1820&epage=1842
Current Topics In Medicinal Chemistry, 2013, vol. 13, num. 15, p. 1820-1842
dc.rights.none.fl_str_mv (c) Bentham Science Publishers, 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Bentham Science Publishers, 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 23 p.
application/pdf
dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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