Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors

Background: The amyloid-β peptide (Aβ42) is the main component of the inter-neuronal amyloid plaques characteristic of Alzheimer's disease (AD). The mechanism by which Aβ42 and other amyloid peptides assemble into insoluble neurotoxic deposits is still not completely understood and multiple fac...

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Authors: Villar Piqué, Anna, Ventura, Salvador|||0000-0002-9652-6351, Espargaró Colomé, Alba, Sabaté Lagunas, Raimon|||0000-0003-3894-2362, Sánchez de Groot, Natalia|||0000-0002-0492-5532
Format: article
Publication Date:2012
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:112879
Online Access:https://ddd.uab.cat/record/112879
https://dx.doi.org/urn:doi:10.1186/1475-2859-11-55
Access Level:Open access
Keyword:Amyloids
Inclusion bodies
Protein folding
Protein aggregation
Metals
Alzheimer
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spelling Using bacterial inclusion bodies to screen for amyloid aggregation inhibitorsVillar Piqué, AnnaVentura, Salvador|||0000-0002-9652-6351Espargaró Colomé, AlbaSabaté Lagunas, Raimon|||0000-0003-3894-2362Sánchez de Groot, Natalia|||0000-0002-0492-5532AmyloidsInclusion bodiesProtein foldingProtein aggregationMetalsAlzheimerBackground: The amyloid-β peptide (Aβ42) is the main component of the inter-neuronal amyloid plaques characteristic of Alzheimer's disease (AD). The mechanism by which Aβ42 and other amyloid peptides assemble into insoluble neurotoxic deposits is still not completely understood and multiple factors have been reported to trigger their formation. In particular, the presence of endogenous metal ions has been linked to the pathogenesis of AD and other neurodegenerative disorders. Results: Here we describe a rapid and high-throughput screening method to identify molecules able to modulate amyloid aggregation. The approach exploits the inclusion bodies (IBs) formed by Aβ42 when expressed in bacteria. We have shown previously that these aggregates retain amyloid structural and functional properties. In the present work, we demonstrate that their in vitro refolding is selectively sensitive to the presence of aggregation-promoting metal ions, allowing the detection of inhibitors of metal-promoted amyloid aggregation with potential therapeutic interest. Conclusions: Because IBs can be produced at high levels and easily purified, the method overcomes one of the main limitations in screens to detect amyloid modulators: the use of expensive and usually highly insoluble synthetic peptides. 22012-01-0120122012-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/112879https://dx.doi.org/urn:doi:10.1186/1475-2859-11-55reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/2.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1128792026-06-06T12:50:31Z
dc.title.none.fl_str_mv Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
title Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
spellingShingle Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
Villar Piqué, Anna
Amyloids
Inclusion bodies
Protein folding
Protein aggregation
Metals
Alzheimer
title_short Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
title_full Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
title_fullStr Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
title_full_unstemmed Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
title_sort Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors
dc.creator.none.fl_str_mv Villar Piqué, Anna
Ventura, Salvador|||0000-0002-9652-6351
Espargaró Colomé, Alba
Sabaté Lagunas, Raimon|||0000-0003-3894-2362
Sánchez de Groot, Natalia|||0000-0002-0492-5532
author Villar Piqué, Anna
author_facet Villar Piqué, Anna
Ventura, Salvador|||0000-0002-9652-6351
Espargaró Colomé, Alba
Sabaté Lagunas, Raimon|||0000-0003-3894-2362
Sánchez de Groot, Natalia|||0000-0002-0492-5532
author_role author
author2 Ventura, Salvador|||0000-0002-9652-6351
Espargaró Colomé, Alba
Sabaté Lagunas, Raimon|||0000-0003-3894-2362
Sánchez de Groot, Natalia|||0000-0002-0492-5532
author2_role author
author
author
author
dc.subject.none.fl_str_mv Amyloids
Inclusion bodies
Protein folding
Protein aggregation
Metals
Alzheimer
topic Amyloids
Inclusion bodies
Protein folding
Protein aggregation
Metals
Alzheimer
description Background: The amyloid-β peptide (Aβ42) is the main component of the inter-neuronal amyloid plaques characteristic of Alzheimer's disease (AD). The mechanism by which Aβ42 and other amyloid peptides assemble into insoluble neurotoxic deposits is still not completely understood and multiple factors have been reported to trigger their formation. In particular, the presence of endogenous metal ions has been linked to the pathogenesis of AD and other neurodegenerative disorders. Results: Here we describe a rapid and high-throughput screening method to identify molecules able to modulate amyloid aggregation. The approach exploits the inclusion bodies (IBs) formed by Aβ42 when expressed in bacteria. We have shown previously that these aggregates retain amyloid structural and functional properties. In the present work, we demonstrate that their in vitro refolding is selectively sensitive to the presence of aggregation-promoting metal ions, allowing the detection of inhibitors of metal-promoted amyloid aggregation with potential therapeutic interest. Conclusions: Because IBs can be produced at high levels and easily purified, the method overcomes one of the main limitations in screens to detect amyloid modulators: the use of expensive and usually highly insoluble synthetic peptides.
publishDate 2012
dc.date.none.fl_str_mv 2
2012-01-01
2012
2012-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/112879
https://dx.doi.org/urn:doi:10.1186/1475-2859-11-55
url https://ddd.uab.cat/record/112879
https://dx.doi.org/urn:doi:10.1186/1475-2859-11-55
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/2.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/2.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
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