Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation

Autores
Torres Bugeau, Clarisa Maria; Avila, Cesar Luis; Raisman Vozari, Rita; Papy Garcia, Dulce; Itri, Rosangela; Barbosa, Leandro R. S.; Cortez, Leonardo; Sim, Valerie L.; Chehin, Rosana Nieves
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lewy bodies and Lewy neurites, neuropathological hallmarks of several neurological diseases, are mainly made of filamentous assemblies of α-synuclein. However, other macromolecules including Tau, ubiquitin, glyceraldehyde-3-phosphate dehydrogenase, and glycosaminoglycans are routinely found associated with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that can form fibrillar aggregates in the presence of acidic membranes, but its role in Parkinson disease is still unknown. In this work, the ability of heparin to trigger the amyloid aggregation of this protein at physiological conditions of pH and temperature is demonstrated by infrared and fluorescence spectroscopy, dynamic light scattering, small angle x-ray scattering, circular dichroism, and fluorescence microscopy. Aggregation proceeds through the formation of short rod-like oligomers, which elongates in one dimension. Heparan sulfate was also capable of inducing glyceraldehyde-3-phosphate dehydrogenase aggregation, but chondroitin sulfates A, B, and C together with dextran sulfate had a negligible effect. Aided with molecular docking simulations, a putative binding site on the protein is proposed providing a rational explanation for the structural specificity of heparin and heparan sulfate. Finally, it is demonstrated that in vitro the early oligomers present in the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote α-synuclein aggregation. Taking into account the toxicity of α-synuclein prefibrillar species, the heparin-induced glyceraldehyde-3-phosphate dehydrogenase early oligomers might come in useful as a novel therapeutic strategy in Parkinson disease and other synucleinopathies. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Fil: Torres Bugeau, Clarisa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Avila, Cesar Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Raisman Vozari, Rita. Inserm; Francia
Fil: Papy Garcia, Dulce. Université Paris Est Crétei; Francia
Fil: Itri, Rosangela. Universidade de Sao Paulo; Brasil
Fil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; Brasil
Fil: Cortez, Leonardo. University of Alberta; Canadá
Fil: Sim, Valerie L.. University of Alberta; Canadá
Fil: Chehin, Rosana Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Materia
Alpha-Synuclein
Amyloid
Glycosaminoglycan
Heparin
Parkinson Disease
Glyceraldehyde-3-phosphate Dehydrogenase Oligomers
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:11336/61811
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/61811
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregationTorres Bugeau, Clarisa MariaAvila, Cesar LuisRaisman Vozari, RitaPapy Garcia, DulceItri, RosangelaBarbosa, Leandro R. S.Cortez, LeonardoSim, Valerie L.Chehin, Rosana NievesAlpha-SynucleinAmyloidGlycosaminoglycanHeparinParkinson DiseaseGlyceraldehyde-3-phosphate Dehydrogenase Oligomershttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Lewy bodies and Lewy neurites, neuropathological hallmarks of several neurological diseases, are mainly made of filamentous assemblies of α-synuclein. However, other macromolecules including Tau, ubiquitin, glyceraldehyde-3-phosphate dehydrogenase, and glycosaminoglycans are routinely found associated with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that can form fibrillar aggregates in the presence of acidic membranes, but its role in Parkinson disease is still unknown. In this work, the ability of heparin to trigger the amyloid aggregation of this protein at physiological conditions of pH and temperature is demonstrated by infrared and fluorescence spectroscopy, dynamic light scattering, small angle x-ray scattering, circular dichroism, and fluorescence microscopy. Aggregation proceeds through the formation of short rod-like oligomers, which elongates in one dimension. Heparan sulfate was also capable of inducing glyceraldehyde-3-phosphate dehydrogenase aggregation, but chondroitin sulfates A, B, and C together with dextran sulfate had a negligible effect. Aided with molecular docking simulations, a putative binding site on the protein is proposed providing a rational explanation for the structural specificity of heparin and heparan sulfate. Finally, it is demonstrated that in vitro the early oligomers present in the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote α-synuclein aggregation. Taking into account the toxicity of α-synuclein prefibrillar species, the heparin-induced glyceraldehyde-3-phosphate dehydrogenase early oligomers might come in useful as a novel therapeutic strategy in Parkinson disease and other synucleinopathies. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.Fil: Torres Bugeau, Clarisa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Avila, Cesar Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Raisman Vozari, Rita. Inserm; FranciaFil: Papy Garcia, Dulce. Université Paris Est Crétei; FranciaFil: Itri, Rosangela. Universidade de Sao Paulo; BrasilFil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; BrasilFil: Cortez, Leonardo. University of Alberta; CanadáFil: Sim, Valerie L.. University of Alberta; CanadáFil: Chehin, Rosana Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaAmerican Society for Biochemistry and Molecular Biology2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/61811Torres Bugeau, Clarisa Maria; Avila, Cesar Luis; Raisman Vozari, Rita; Papy Garcia, Dulce; Itri, Rosangela; et al.; Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 287; 4; 1-2012; 2398-24090021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M111.303503info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/287/4/2398info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:38Zoai:ri.conicet.gov.ar:11336/61811instacron: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 09:56:38.507CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
title Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
spellingShingle Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
Torres Bugeau, Clarisa Maria
Alpha-Synuclein
Amyloid
Glycosaminoglycan
Heparin
Parkinson Disease
Glyceraldehyde-3-phosphate Dehydrogenase Oligomers
title_short Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
title_full Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
title_fullStr Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
title_full_unstemmed Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
title_sort Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation
dc.creator.none.fl_str_mv Torres Bugeau, Clarisa Maria
Avila, Cesar Luis
Raisman Vozari, Rita
Papy Garcia, Dulce
Itri, Rosangela
Barbosa, Leandro R. S.
Cortez, Leonardo
Sim, Valerie L.
Chehin, Rosana Nieves
author Torres Bugeau, Clarisa Maria
author_facet Torres Bugeau, Clarisa Maria
Avila, Cesar Luis
Raisman Vozari, Rita
Papy Garcia, Dulce
Itri, Rosangela
Barbosa, Leandro R. S.
Cortez, Leonardo
Sim, Valerie L.
Chehin, Rosana Nieves
author_role author
author2 Avila, Cesar Luis
Raisman Vozari, Rita
Papy Garcia, Dulce
Itri, Rosangela
Barbosa, Leandro R. S.
Cortez, Leonardo
Sim, Valerie L.
Chehin, Rosana Nieves
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alpha-Synuclein
Amyloid
Glycosaminoglycan
Heparin
Parkinson Disease
Glyceraldehyde-3-phosphate Dehydrogenase Oligomers
topic Alpha-Synuclein
Amyloid
Glycosaminoglycan
Heparin
Parkinson Disease
Glyceraldehyde-3-phosphate Dehydrogenase Oligomers
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lewy bodies and Lewy neurites, neuropathological hallmarks of several neurological diseases, are mainly made of filamentous assemblies of α-synuclein. However, other macromolecules including Tau, ubiquitin, glyceraldehyde-3-phosphate dehydrogenase, and glycosaminoglycans are routinely found associated with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that can form fibrillar aggregates in the presence of acidic membranes, but its role in Parkinson disease is still unknown. In this work, the ability of heparin to trigger the amyloid aggregation of this protein at physiological conditions of pH and temperature is demonstrated by infrared and fluorescence spectroscopy, dynamic light scattering, small angle x-ray scattering, circular dichroism, and fluorescence microscopy. Aggregation proceeds through the formation of short rod-like oligomers, which elongates in one dimension. Heparan sulfate was also capable of inducing glyceraldehyde-3-phosphate dehydrogenase aggregation, but chondroitin sulfates A, B, and C together with dextran sulfate had a negligible effect. Aided with molecular docking simulations, a putative binding site on the protein is proposed providing a rational explanation for the structural specificity of heparin and heparan sulfate. Finally, it is demonstrated that in vitro the early oligomers present in the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote α-synuclein aggregation. Taking into account the toxicity of α-synuclein prefibrillar species, the heparin-induced glyceraldehyde-3-phosphate dehydrogenase early oligomers might come in useful as a novel therapeutic strategy in Parkinson disease and other synucleinopathies. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Fil: Torres Bugeau, Clarisa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Avila, Cesar Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Raisman Vozari, Rita. Inserm; Francia
Fil: Papy Garcia, Dulce. Université Paris Est Crétei; Francia
Fil: Itri, Rosangela. Universidade de Sao Paulo; Brasil
Fil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; Brasil
Fil: Cortez, Leonardo. University of Alberta; Canadá
Fil: Sim, Valerie L.. University of Alberta; Canadá
Fil: Chehin, Rosana Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
description Lewy bodies and Lewy neurites, neuropathological hallmarks of several neurological diseases, are mainly made of filamentous assemblies of α-synuclein. However, other macromolecules including Tau, ubiquitin, glyceraldehyde-3-phosphate dehydrogenase, and glycosaminoglycans are routinely found associated with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that can form fibrillar aggregates in the presence of acidic membranes, but its role in Parkinson disease is still unknown. In this work, the ability of heparin to trigger the amyloid aggregation of this protein at physiological conditions of pH and temperature is demonstrated by infrared and fluorescence spectroscopy, dynamic light scattering, small angle x-ray scattering, circular dichroism, and fluorescence microscopy. Aggregation proceeds through the formation of short rod-like oligomers, which elongates in one dimension. Heparan sulfate was also capable of inducing glyceraldehyde-3-phosphate dehydrogenase aggregation, but chondroitin sulfates A, B, and C together with dextran sulfate had a negligible effect. Aided with molecular docking simulations, a putative binding site on the protein is proposed providing a rational explanation for the structural specificity of heparin and heparan sulfate. Finally, it is demonstrated that in vitro the early oligomers present in the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote α-synuclein aggregation. Taking into account the toxicity of α-synuclein prefibrillar species, the heparin-induced glyceraldehyde-3-phosphate dehydrogenase early oligomers might come in useful as a novel therapeutic strategy in Parkinson disease and other synucleinopathies. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/61811
Torres Bugeau, Clarisa Maria; Avila, Cesar Luis; Raisman Vozari, Rita; Papy Garcia, Dulce; Itri, Rosangela; et al.; Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 287; 4; 1-2012; 2398-2409
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/61811
identifier_str_mv Torres Bugeau, Clarisa Maria; Avila, Cesar Luis; Raisman Vozari, Rita; Papy Garcia, Dulce; Itri, Rosangela; et al.; Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication in α-synuclein aggregation; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 287; 4; 1-2012; 2398-2409
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M111.303503
info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/287/4/2398
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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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