Modulation of alpha-synuclein aggregation by dopamine analogs

Autores
Latawiec, Diane; Herrera, Fernando Enrique; Bek, Alpan; Losasso, Valeria; Candotti, Michela; Benetti, Federico; Carlino, Elvio; Kranjc, Agata; Lazzarino, Marco; Gustincich, Stefano; Carloni, Paolo; Legname, Giuseppe
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit α-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of α-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to α-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein. © 2010 Latawiec et al.
Fil: Latawiec, Diane. Italian Institute of Technology; Italia
Fil: Herrera, Fernando Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Italian Institute of Technology; Italia
Fil: Bek, Alpan. Center for Molecular Biomedicine; Italia
Fil: Losasso, Valeria. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Candotti, Michela. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Benetti, Federico. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Carlino, Elvio. TASC-INFM National Laboratory; Italia
Fil: Kranjc, Agata. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Lazzarino, Marco. TASC-INFM National Laboratory; Italia
Fil: Gustincich, Stefano. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Carloni, Paolo. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Legname, Giuseppe. Scuola Internazionale Superiore di Studi Avanzati; Italia
Materia
Alpha
Synuclein
Dopamine
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66683
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/66683
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Modulation of alpha-synuclein aggregation by dopamine analogsLatawiec, DianeHerrera, Fernando EnriqueBek, AlpanLosasso, ValeriaCandotti, MichelaBenetti, FedericoCarlino, ElvioKranjc, AgataLazzarino, MarcoGustincich, StefanoCarloni, PaoloLegname, GiuseppeAlphaSynucleinDopaminehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit α-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of α-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to α-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein. © 2010 Latawiec et al.Fil: Latawiec, Diane. Italian Institute of Technology; ItaliaFil: Herrera, Fernando Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Italian Institute of Technology; ItaliaFil: Bek, Alpan. Center for Molecular Biomedicine; ItaliaFil: Losasso, Valeria. Scuola Internazionale Superiore di Studi Avanzati; ItaliaFil: Candotti, Michela. Scuola Internazionale Superiore di Studi Avanzati; ItaliaFil: Benetti, Federico. Scuola Internazionale Superiore di Studi Avanzati; ItaliaFil: Carlino, Elvio. TASC-INFM National Laboratory; ItaliaFil: Kranjc, Agata. Scuola Internazionale Superiore di Studi Avanzati; ItaliaFil: Lazzarino, Marco. TASC-INFM National Laboratory; ItaliaFil: Gustincich, Stefano. Scuola Internazionale Superiore di Studi Avanzati; ItaliaFil: Carloni, Paolo. Scuola Internazionale Superiore di Studi Avanzati; ItaliaFil: Legname, Giuseppe. Scuola Internazionale Superiore di Studi Avanzati; ItaliaPublic Library of Science2010-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66683Latawiec, Diane; Herrera, Fernando Enrique; Bek, Alpan; Losasso, Valeria; Candotti, Michela; et al.; Modulation of alpha-synuclein aggregation by dopamine analogs; Public Library of Science; Plos One; 5; 2; 2-2010; 1-81932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0009234info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009234info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:12Zoai:ri.conicet.gov.ar:11336/66683instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:12.914CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulation of alpha-synuclein aggregation by dopamine analogs
title Modulation of alpha-synuclein aggregation by dopamine analogs
spellingShingle Modulation of alpha-synuclein aggregation by dopamine analogs
Latawiec, Diane
Alpha
Synuclein
Dopamine
title_short Modulation of alpha-synuclein aggregation by dopamine analogs
title_full Modulation of alpha-synuclein aggregation by dopamine analogs
title_fullStr Modulation of alpha-synuclein aggregation by dopamine analogs
title_full_unstemmed Modulation of alpha-synuclein aggregation by dopamine analogs
title_sort Modulation of alpha-synuclein aggregation by dopamine analogs
dc.creator.none.fl_str_mv Latawiec, Diane
Herrera, Fernando Enrique
Bek, Alpan
Losasso, Valeria
Candotti, Michela
Benetti, Federico
Carlino, Elvio
Kranjc, Agata
Lazzarino, Marco
Gustincich, Stefano
Carloni, Paolo
Legname, Giuseppe
author Latawiec, Diane
author_facet Latawiec, Diane
Herrera, Fernando Enrique
Bek, Alpan
Losasso, Valeria
Candotti, Michela
Benetti, Federico
Carlino, Elvio
Kranjc, Agata
Lazzarino, Marco
Gustincich, Stefano
Carloni, Paolo
Legname, Giuseppe
author_role author
author2 Herrera, Fernando Enrique
Bek, Alpan
Losasso, Valeria
Candotti, Michela
Benetti, Federico
Carlino, Elvio
Kranjc, Agata
Lazzarino, Marco
Gustincich, Stefano
Carloni, Paolo
Legname, Giuseppe
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alpha
Synuclein
Dopamine
topic Alpha
Synuclein
Dopamine
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit α-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of α-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to α-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein. © 2010 Latawiec et al.
Fil: Latawiec, Diane. Italian Institute of Technology; Italia
Fil: Herrera, Fernando Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Italian Institute of Technology; Italia
Fil: Bek, Alpan. Center for Molecular Biomedicine; Italia
Fil: Losasso, Valeria. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Candotti, Michela. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Benetti, Federico. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Carlino, Elvio. TASC-INFM National Laboratory; Italia
Fil: Kranjc, Agata. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Lazzarino, Marco. TASC-INFM National Laboratory; Italia
Fil: Gustincich, Stefano. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Carloni, Paolo. Scuola Internazionale Superiore di Studi Avanzati; Italia
Fil: Legname, Giuseppe. Scuola Internazionale Superiore di Studi Avanzati; Italia
description The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit α-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of α-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to α-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein. © 2010 Latawiec et al.
publishDate 2010
dc.date.none.fl_str_mv 2010-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/66683
Latawiec, Diane; Herrera, Fernando Enrique; Bek, Alpan; Losasso, Valeria; Candotti, Michela; et al.; Modulation of alpha-synuclein aggregation by dopamine analogs; Public Library of Science; Plos One; 5; 2; 2-2010; 1-8
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66683
identifier_str_mv Latawiec, Diane; Herrera, Fernando Enrique; Bek, Alpan; Losasso, Valeria; Candotti, Michela; et al.; Modulation of alpha-synuclein aggregation by dopamine analogs; Public Library of Science; Plos One; 5; 2; 2-2010; 1-8
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0009234
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009234
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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