Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure

Autores
Celej, Maria Soledad; Sarroukh, R.,; Goormaghtigh, E.,; Fidelio, Gerardo Daniel; Ruysschaert, Jean-Marie; Raussens, Vincent
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β- sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers. © The Authors Journal compilation © 2012 Biochemical Society.
Fil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Sarroukh, R.,. Université Libre de Bruxelles; Bélgica
Fil: Goormaghtigh, E.,. Université Libre de Bruxelles; Bélgica
Fil: Fidelio, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Ruysschaert, Jean-Marie. Université Libre de Bruxelles; Bélgica
Fil: Raussens, Vincent. Université Libre de Bruxelles; Bélgica
Materia
Α-SYNUCLEIN
AMYLOID OLIGOMER
AMYLOIDOGENESIS
PARKINSON'S DISEASE
SECONDARY STRUCTURE
STRUCTURE-TOXICITY RELATIONSHIP
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:11336/198102
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/198102
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structureCelej, Maria SoledadSarroukh, R.,Goormaghtigh, E.,Fidelio, Gerardo DanielRuysschaert, Jean-MarieRaussens, VincentΑ-SYNUCLEINAMYLOID OLIGOMERAMYLOIDOGENESISPARKINSON'S DISEASESECONDARY STRUCTURESTRUCTURE-TOXICITY RELATIONSHIPhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β- sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers. © The Authors Journal compilation © 2012 Biochemical Society.Fil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Sarroukh, R.,. Université Libre de Bruxelles; BélgicaFil: Goormaghtigh, E.,. Université Libre de Bruxelles; BélgicaFil: Fidelio, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Ruysschaert, Jean-Marie. Université Libre de Bruxelles; BélgicaFil: Raussens, Vincent. Université Libre de Bruxelles; BélgicaJournal of the Serbian Chemical Society2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/198102Celej, Maria Soledad; Sarroukh, R.,; Goormaghtigh, E.,; Fidelio, Gerardo Daniel; Ruysschaert, Jean-Marie; et al.; Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure; Journal of the Serbian Chemical Society; Biochemical Journal; 443; 3; 5-2012; 719-7260264-60211470-8728CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20111924info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/22316405/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:51Zoai:ri.conicet.gov.ar:11336/198102instacron: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 10:05:51.293CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
title Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
spellingShingle Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
Celej, Maria Soledad
Α-SYNUCLEIN
AMYLOID OLIGOMER
AMYLOIDOGENESIS
PARKINSON'S DISEASE
SECONDARY STRUCTURE
STRUCTURE-TOXICITY RELATIONSHIP
title_short Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
title_full Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
title_fullStr Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
title_full_unstemmed Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
title_sort Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
dc.creator.none.fl_str_mv Celej, Maria Soledad
Sarroukh, R.,
Goormaghtigh, E.,
Fidelio, Gerardo Daniel
Ruysschaert, Jean-Marie
Raussens, Vincent
author Celej, Maria Soledad
author_facet Celej, Maria Soledad
Sarroukh, R.,
Goormaghtigh, E.,
Fidelio, Gerardo Daniel
Ruysschaert, Jean-Marie
Raussens, Vincent
author_role author
author2 Sarroukh, R.,
Goormaghtigh, E.,
Fidelio, Gerardo Daniel
Ruysschaert, Jean-Marie
Raussens, Vincent
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Α-SYNUCLEIN
AMYLOID OLIGOMER
AMYLOIDOGENESIS
PARKINSON'S DISEASE
SECONDARY STRUCTURE
STRUCTURE-TOXICITY RELATIONSHIP
topic Α-SYNUCLEIN
AMYLOID OLIGOMER
AMYLOIDOGENESIS
PARKINSON'S DISEASE
SECONDARY STRUCTURE
STRUCTURE-TOXICITY RELATIONSHIP
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β- sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers. © The Authors Journal compilation © 2012 Biochemical Society.
Fil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Sarroukh, R.,. Université Libre de Bruxelles; Bélgica
Fil: Goormaghtigh, E.,. Université Libre de Bruxelles; Bélgica
Fil: Fidelio, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Ruysschaert, Jean-Marie. Université Libre de Bruxelles; Bélgica
Fil: Raussens, Vincent. Université Libre de Bruxelles; Bélgica
description Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β- sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers. © The Authors Journal compilation © 2012 Biochemical Society.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
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/11336/198102
Celej, Maria Soledad; Sarroukh, R.,; Goormaghtigh, E.,; Fidelio, Gerardo Daniel; Ruysschaert, Jean-Marie; et al.; Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure; Journal of the Serbian Chemical Society; Biochemical Journal; 443; 3; 5-2012; 719-726
0264-6021
1470-8728
CONICET Digital
CONICET
url http://hdl.handle.net/11336/198102
identifier_str_mv Celej, Maria Soledad; Sarroukh, R.,; Goormaghtigh, E.,; Fidelio, Gerardo Daniel; Ruysschaert, Jean-Marie; et al.; Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure; Journal of the Serbian Chemical Society; Biochemical Journal; 443; 3; 5-2012; 719-726
0264-6021
1470-8728
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20111924
info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/22316405/
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 Journal of the Serbian Chemical Society
publisher.none.fl_str_mv Journal of the Serbian Chemical Society
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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