Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease

Autores
Binolfi, Andrés; Quintanar, Liliana; Bertoncini, Carlos Walter; Griesinger, C; Fernandez, Claudio Oscar
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alpha-synuclein (AS) aggregation is associated with neurodegeneration in Parkinson's disease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS-metal interactions and their effect on AS aggregation constitutes a key step toward understanding the role of metal ions in AS amyloid formation and neurodegeneration. This work provides a comprehensive review of recent advances attained in the bioinorganic chemistry of AS amyloid diseases. A hierarchy in AS-metal ion interactions has been established: while the physiologically relevant divalent metal ions iron and manganese interact at a non-specific, low-affinity binding interface in the C-terminus of AS, copper binds with high affinity at the N-terminal region and it is the most effective metal ion in accelerating AS filament assembly. The strong link between metal binding specificity and its impact on aggregation is discussed here on a mechanistic basis. A detailed description of the structural features and coordination environments of copper to AS is presented and discussed in the context of oxidative cellular events that might lead to the development of PD. Overall, the research observations presented here support the notion that perturbations in copper metabolism may be a common upstream event in the pathogenesis of neurodegenerative processes.
Fil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Física; México
Fil: Bertoncini, Carlos Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Griesinger, C. Max Planck Institute for Biophysical Chemistry; Alemania
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Materia
alpha-synuclein
copper
chemistry
neurodegeneration
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:11336/268471
Acceder
id CONICETDig_0a907840992a8b611cf51406dfcebaa5
oai_identifier_str oai:ri.conicet.gov.ar:11336/268471
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's diseaseBinolfi, AndrésQuintanar, LilianaBertoncini, Carlos WalterGriesinger, CFernandez, Claudio Oscaralpha-synucleincopperchemistryneurodegenerationhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Alpha-synuclein (AS) aggregation is associated with neurodegeneration in Parkinson's disease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS-metal interactions and their effect on AS aggregation constitutes a key step toward understanding the role of metal ions in AS amyloid formation and neurodegeneration. This work provides a comprehensive review of recent advances attained in the bioinorganic chemistry of AS amyloid diseases. A hierarchy in AS-metal ion interactions has been established: while the physiologically relevant divalent metal ions iron and manganese interact at a non-specific, low-affinity binding interface in the C-terminus of AS, copper binds with high affinity at the N-terminal region and it is the most effective metal ion in accelerating AS filament assembly. The strong link between metal binding specificity and its impact on aggregation is discussed here on a mechanistic basis. A detailed description of the structural features and coordination environments of copper to AS is presented and discussed in the context of oxidative cellular events that might lead to the development of PD. Overall, the research observations presented here support the notion that perturbations in copper metabolism may be a common upstream event in the pathogenesis of neurodegenerative processes.Fil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Física; MéxicoFil: Bertoncini, Carlos Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Griesinger, C. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaElsevier Science SA2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/268471Binolfi, Andrés; Quintanar, Liliana; Bertoncini, Carlos Walter; Griesinger, C; Fernandez, Claudio Oscar; Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease; Elsevier Science SA; Coordination Chemistry Reviews; 256; 19-20; 10-2012; 2188-22010010-8545CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0010854512001221info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ccr.2012.05.004info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:38Zoai:ri.conicet.gov.ar:11336/268471instacron: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 09:53:38.577CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
title Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
spellingShingle Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
Binolfi, Andrés
alpha-synuclein
copper
chemistry
neurodegeneration
title_short Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
title_full Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
title_fullStr Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
title_full_unstemmed Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
title_sort Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease
dc.creator.none.fl_str_mv Binolfi, Andrés
Quintanar, Liliana
Bertoncini, Carlos Walter
Griesinger, C
Fernandez, Claudio Oscar
author Binolfi, Andrés
author_facet Binolfi, Andrés
Quintanar, Liliana
Bertoncini, Carlos Walter
Griesinger, C
Fernandez, Claudio Oscar
author_role author
author2 Quintanar, Liliana
Bertoncini, Carlos Walter
Griesinger, C
Fernandez, Claudio Oscar
author2_role author
author
author
author
dc.subject.none.fl_str_mv alpha-synuclein
copper
chemistry
neurodegeneration
topic alpha-synuclein
copper
chemistry
neurodegeneration
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alpha-synuclein (AS) aggregation is associated with neurodegeneration in Parkinson's disease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS-metal interactions and their effect on AS aggregation constitutes a key step toward understanding the role of metal ions in AS amyloid formation and neurodegeneration. This work provides a comprehensive review of recent advances attained in the bioinorganic chemistry of AS amyloid diseases. A hierarchy in AS-metal ion interactions has been established: while the physiologically relevant divalent metal ions iron and manganese interact at a non-specific, low-affinity binding interface in the C-terminus of AS, copper binds with high affinity at the N-terminal region and it is the most effective metal ion in accelerating AS filament assembly. The strong link between metal binding specificity and its impact on aggregation is discussed here on a mechanistic basis. A detailed description of the structural features and coordination environments of copper to AS is presented and discussed in the context of oxidative cellular events that might lead to the development of PD. Overall, the research observations presented here support the notion that perturbations in copper metabolism may be a common upstream event in the pathogenesis of neurodegenerative processes.
Fil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Física; México
Fil: Bertoncini, Carlos Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Griesinger, C. Max Planck Institute for Biophysical Chemistry; Alemania
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
description Alpha-synuclein (AS) aggregation is associated with neurodegeneration in Parkinson's disease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS-metal interactions and their effect on AS aggregation constitutes a key step toward understanding the role of metal ions in AS amyloid formation and neurodegeneration. This work provides a comprehensive review of recent advances attained in the bioinorganic chemistry of AS amyloid diseases. A hierarchy in AS-metal ion interactions has been established: while the physiologically relevant divalent metal ions iron and manganese interact at a non-specific, low-affinity binding interface in the C-terminus of AS, copper binds with high affinity at the N-terminal region and it is the most effective metal ion in accelerating AS filament assembly. The strong link between metal binding specificity and its impact on aggregation is discussed here on a mechanistic basis. A detailed description of the structural features and coordination environments of copper to AS is presented and discussed in the context of oxidative cellular events that might lead to the development of PD. Overall, the research observations presented here support the notion that perturbations in copper metabolism may be a common upstream event in the pathogenesis of neurodegenerative processes.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
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/11336/268471
Binolfi, Andrés; Quintanar, Liliana; Bertoncini, Carlos Walter; Griesinger, C; Fernandez, Claudio Oscar; Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease; Elsevier Science SA; Coordination Chemistry Reviews; 256; 19-20; 10-2012; 2188-2201
0010-8545
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268471
identifier_str_mv Binolfi, Andrés; Quintanar, Liliana; Bertoncini, Carlos Walter; Griesinger, C; Fernandez, Claudio Oscar; Bioinorganic chemistry of copper coordination to alpha-synuclein: Relevance to Parkinson's disease; Elsevier Science SA; Coordination Chemistry Reviews; 256; 19-20; 10-2012; 2188-2201
0010-8545
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0010854512001221
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ccr.2012.05.004
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
dc.publisher.none.fl_str_mv Elsevier Science SA
publisher.none.fl_str_mv Elsevier Science SA
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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