ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization

Peña Díaz, Samuel|||0000-0002-2902-823X; Pujols Pujol, Jordi|||0000-0001-9424-5866; Conde Giménez, María|||0000-0003-4358-9110; Carija, Anita|||0000-0001-5972-7448; Dalfo, Esther|||0000-0003-4677-8515; García, Jesús; Navarro, Susanna|||0000-0001-8160-9536; Garcia de Carvalho Pinheiro, Francisca|||0000-0003-3778-1528; Santos Suárez, Jaime|||0000-0001-9045-7765; Salvatella, Xavier|||0000-0002-8371-4185; Sancho Sanz, Javier|||0000-0002-2879-9200; Ventura, Salvador|||0000-0002-9652-6351

ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization

α-Synuclein (α-Syn) forms toxic intracellular protein inclusions and transmissible amyloid structures in Parkinson's disease (PD). Preventing α-Syn self-assembly has become one of the most promising approaches in the search for disease-modifying treatments for this neurodegenerative disorder. H...

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Autores:	Peña Díaz, Samuel\|\|\|0000-0002-2902-823X, Pujols Pujol, Jordi\|\|\|0000-0001-9424-5866, Conde Giménez, María\|\|\|0000-0003-4358-9110, Carija, Anita\|\|\|0000-0001-5972-7448, Dalfo, Esther\|\|\|0000-0003-4677-8515, García, Jesús, Navarro, Susanna\|\|\|0000-0001-8160-9536, Garcia de Carvalho Pinheiro, Francisca\|\|\|0000-0003-3778-1528, Santos Suárez, Jaime\|\|\|0000-0001-9045-7765, Salvatella, Xavier\|\|\|0000-0002-8371-4185, Sancho Sanz, Javier\|\|\|0000-0002-2879-9200, Ventura, Salvador\|\|\|0000-0002-9652-6351
Tipo de recurso:	artículo
Fecha de publicación:	2019
País:	España
Institución:	Universitat Autònoma de Barcelona
Repositorio:	Dipòsit Digital de Documents de la UAB
Idioma:	inglés
OAI Identifier:	oai:ddd.uab.cat:223739
Acceso en línea:	https://ddd.uab.cat/record/223739 https://dx.doi.org/urn:doi:10.3389/fnmol.2019.00306
Access Level:	acceso abierto
Palabra clave:	Parkinson's disease α-synuclein Amyloid Protein aggregation Aggregation inhibitor Caenorhabditis elegans Neurodegeneration

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spelling	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerizationPeña Díaz, Samuel\|\|\|0000-0002-2902-823XPujols Pujol, Jordi\|\|\|0000-0001-9424-5866Conde Giménez, María\|\|\|0000-0003-4358-9110Carija, Anita\|\|\|0000-0001-5972-7448Dalfo, Esther\|\|\|0000-0003-4677-8515García, JesúsNavarro, Susanna\|\|\|0000-0001-8160-9536Garcia de Carvalho Pinheiro, Francisca\|\|\|0000-0003-3778-1528Santos Suárez, Jaime\|\|\|0000-0001-9045-7765Salvatella, Xavier\|\|\|0000-0002-8371-4185Sancho Sanz, Javier\|\|\|0000-0002-2879-9200Ventura, Salvador\|\|\|0000-0002-9652-6351Parkinson's diseaseα-synucleinAmyloidProtein aggregationAggregation inhibitorCaenorhabditis elegansNeurodegenerationα-Synuclein (α-Syn) forms toxic intracellular protein inclusions and transmissible amyloid structures in Parkinson's disease (PD). Preventing α-Syn self-assembly has become one of the most promising approaches in the search for disease-modifying treatments for this neurodegenerative disorder. Here, we describe the capacity of a small molecule (ZPD-2), identified after a high-throughput screening, to inhibit α-Syn aggregation. ZPD-2 inhibits the aggregation of wild-type α-Syn and the A30P and H50Q familial variants in vitro at substoichiometric compound:protein ratios. In addition, the molecule prevents the spreading of α-Syn seeds in protein misfolding cyclic amplification assays. ZPD-2 is active against different α-Syn strains and blocks their seeded polymerization. Treating with ZPD-2 two different PD Caenorhabditis elegans models that express α-Syn either in muscle or in dopaminergic (DA) neurons substantially reduces the number of α-Syn inclusions and decreases synuclein-induced DA neurons degeneration. Overall, ZPD-2 is a hit compound worth to be explored in order to develop lead molecules for therapeutic intervention in PD. 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/223739https://dx.doi.org/urn:doi:10.3389/fnmol.2019.00306reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 648201Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BIO2015-70092-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-78310-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2016-78232-Popen 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/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2237392026-06-06T12:50:31Z
dc.title.none.fl_str_mv	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
title	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
spellingShingle	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization Peña Díaz, Samuel\|\|\|0000-0002-2902-823X Parkinson's disease α-synuclein Amyloid Protein aggregation Aggregation inhibitor Caenorhabditis elegans Neurodegeneration
title_short	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
title_full	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
title_fullStr	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
title_full_unstemmed	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
title_sort	ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization
dc.creator.none.fl_str_mv	Peña Díaz, Samuel\|\|\|0000-0002-2902-823X Pujols Pujol, Jordi\|\|\|0000-0001-9424-5866 Conde Giménez, María\|\|\|0000-0003-4358-9110 Carija, Anita\|\|\|0000-0001-5972-7448 Dalfo, Esther\|\|\|0000-0003-4677-8515 García, Jesús Navarro, Susanna\|\|\|0000-0001-8160-9536 Garcia de Carvalho Pinheiro, Francisca\|\|\|0000-0003-3778-1528 Santos Suárez, Jaime\|\|\|0000-0001-9045-7765 Salvatella, Xavier\|\|\|0000-0002-8371-4185 Sancho Sanz, Javier\|\|\|0000-0002-2879-9200 Ventura, Salvador\|\|\|0000-0002-9652-6351
author	Peña Díaz, Samuel\|\|\|0000-0002-2902-823X
author_facet	Peña Díaz, Samuel\|\|\|0000-0002-2902-823X Pujols Pujol, Jordi\|\|\|0000-0001-9424-5866 Conde Giménez, María\|\|\|0000-0003-4358-9110 Carija, Anita\|\|\|0000-0001-5972-7448 Dalfo, Esther\|\|\|0000-0003-4677-8515 García, Jesús Navarro, Susanna\|\|\|0000-0001-8160-9536 Garcia de Carvalho Pinheiro, Francisca\|\|\|0000-0003-3778-1528 Santos Suárez, Jaime\|\|\|0000-0001-9045-7765 Salvatella, Xavier\|\|\|0000-0002-8371-4185 Sancho Sanz, Javier\|\|\|0000-0002-2879-9200 Ventura, Salvador\|\|\|0000-0002-9652-6351
author_role	author
author2	Pujols Pujol, Jordi\|\|\|0000-0001-9424-5866 Conde Giménez, María\|\|\|0000-0003-4358-9110 Carija, Anita\|\|\|0000-0001-5972-7448 Dalfo, Esther\|\|\|0000-0003-4677-8515 García, Jesús Navarro, Susanna\|\|\|0000-0001-8160-9536 Garcia de Carvalho Pinheiro, Francisca\|\|\|0000-0003-3778-1528 Santos Suárez, Jaime\|\|\|0000-0001-9045-7765 Salvatella, Xavier\|\|\|0000-0002-8371-4185 Sancho Sanz, Javier\|\|\|0000-0002-2879-9200 Ventura, Salvador\|\|\|0000-0002-9652-6351
author2_role	author author author author author author author author author author author
dc.subject.none.fl_str_mv	Parkinson's disease α-synuclein Amyloid Protein aggregation Aggregation inhibitor Caenorhabditis elegans Neurodegeneration
topic	Parkinson's disease α-synuclein Amyloid Protein aggregation Aggregation inhibitor Caenorhabditis elegans Neurodegeneration
description	α-Synuclein (α-Syn) forms toxic intracellular protein inclusions and transmissible amyloid structures in Parkinson's disease (PD). Preventing α-Syn self-assembly has become one of the most promising approaches in the search for disease-modifying treatments for this neurodegenerative disorder. Here, we describe the capacity of a small molecule (ZPD-2), identified after a high-throughput screening, to inhibit α-Syn aggregation. ZPD-2 inhibits the aggregation of wild-type α-Syn and the A30P and H50Q familial variants in vitro at substoichiometric compound:protein ratios. In addition, the molecule prevents the spreading of α-Syn seeds in protein misfolding cyclic amplification assays. ZPD-2 is active against different α-Syn strains and blocks their seeded polymerization. Treating with ZPD-2 two different PD Caenorhabditis elegans models that express α-Syn either in muscle or in dopaminergic (DA) neurons substantially reduces the number of α-Syn inclusions and decreases synuclein-induced DA neurons degeneration. Overall, ZPD-2 is a hit compound worth to be explored in order to develop lead molecules for therapeutic intervention in PD.
publishDate	2019
dc.date.none.fl_str_mv	2 2019-01-01 2019 2019-01-01
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/223739 https://dx.doi.org/urn:doi:10.3389/fnmol.2019.00306
url	https://ddd.uab.cat/record/223739 https://dx.doi.org/urn:doi:10.3389/fnmol.2019.00306
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	European Commission https://doi.org/10.13039/501100000780 648201 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BIO2015-70092-R Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BIO2016-78310-R Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2016-78232-P
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
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/4.0/
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
repository.mail.fl_str_mv
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ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization

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