Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity

Autores
Gallea, Jose Ignacio; Ambroggio, Ernesto Esteban; Vilcaes, Aldo Alejandro; James, Nicholas G.; Jameson, David M.; Celej, Maria Soledad
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The amyloid aggregation of the presynaptic protein α-synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N-terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain-of-toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein-lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides novel insights into how the formation of prefibrillar intermediate species could contribute to neurodegeneration due to a loss-of-function mechanism.
Fil: Gallea, Jose Ignacio. 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: Ambroggio, Ernesto Esteban. 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: Vilcaes, Aldo Alejandro. 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: James, Nicholas G.. University of Hawaii at Manoa; Estados Unidos
Fil: Jameson, David M.. University of Hawaii at Manoa; Estados Unidos
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
Materia
FCS
LIPID-PROTEIN INTERACTION
NEURODEGENERATION
PROTEIN AGGREGATION
SYNUCLEINOPATHIES
TOXIC OLIGOMERS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/95825
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/95825
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivityGallea, Jose IgnacioAmbroggio, Ernesto EstebanVilcaes, Aldo AlejandroJames, Nicholas G.Jameson, David M.Celej, Maria SoledadFCSLIPID-PROTEIN INTERACTIONNEURODEGENERATIONPROTEIN AGGREGATIONSYNUCLEINOPATHIESTOXIC OLIGOMERShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The amyloid aggregation of the presynaptic protein α-synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N-terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain-of-toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein-lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides novel insights into how the formation of prefibrillar intermediate species could contribute to neurodegeneration due to a loss-of-function mechanism.Fil: Gallea, Jose Ignacio. 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: Ambroggio, Ernesto Esteban. 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: Vilcaes, Aldo Alejandro. 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: James, Nicholas G.. University of Hawaii at Manoa; Estados UnidosFil: Jameson, David M.. University of Hawaii at Manoa; Estados UnidosFil: 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; ArgentinaWiley Blackwell Publishing, Inc2018-11info: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/11336/95825Gallea, Jose Ignacio; Ambroggio, Ernesto Esteban; Vilcaes, Aldo Alejandro; James, Nicholas G.; Jameson, David M.; et al.; Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 147; 4; 11-2018; 541-5560022-3042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/jnc.14573info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.14573info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:56Zoai:ri.conicet.gov.ar:11336/95825instacron: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 10:11:57.26CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
title Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
spellingShingle Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
Gallea, Jose Ignacio
FCS
LIPID-PROTEIN INTERACTION
NEURODEGENERATION
PROTEIN AGGREGATION
SYNUCLEINOPATHIES
TOXIC OLIGOMERS
title_short Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
title_full Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
title_fullStr Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
title_full_unstemmed Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
title_sort Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity
dc.creator.none.fl_str_mv Gallea, Jose Ignacio
Ambroggio, Ernesto Esteban
Vilcaes, Aldo Alejandro
James, Nicholas G.
Jameson, David M.
Celej, Maria Soledad
author Gallea, Jose Ignacio
author_facet Gallea, Jose Ignacio
Ambroggio, Ernesto Esteban
Vilcaes, Aldo Alejandro
James, Nicholas G.
Jameson, David M.
Celej, Maria Soledad
author_role author
author2 Ambroggio, Ernesto Esteban
Vilcaes, Aldo Alejandro
James, Nicholas G.
Jameson, David M.
Celej, Maria Soledad
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv FCS
LIPID-PROTEIN INTERACTION
NEURODEGENERATION
PROTEIN AGGREGATION
SYNUCLEINOPATHIES
TOXIC OLIGOMERS
topic FCS
LIPID-PROTEIN INTERACTION
NEURODEGENERATION
PROTEIN AGGREGATION
SYNUCLEINOPATHIES
TOXIC 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 The amyloid aggregation of the presynaptic protein α-synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N-terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain-of-toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein-lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides novel insights into how the formation of prefibrillar intermediate species could contribute to neurodegeneration due to a loss-of-function mechanism.
Fil: Gallea, Jose Ignacio. 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: Ambroggio, Ernesto Esteban. 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: Vilcaes, Aldo Alejandro. 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: James, Nicholas G.. University of Hawaii at Manoa; Estados Unidos
Fil: Jameson, David M.. University of Hawaii at Manoa; Estados Unidos
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
description The amyloid aggregation of the presynaptic protein α-synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N-terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain-of-toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein-lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides novel insights into how the formation of prefibrillar intermediate species could contribute to neurodegeneration due to a loss-of-function mechanism.
publishDate 2018
dc.date.none.fl_str_mv 2018-11
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/11336/95825
Gallea, Jose Ignacio; Ambroggio, Ernesto Esteban; Vilcaes, Aldo Alejandro; James, Nicholas G.; Jameson, David M.; et al.; Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 147; 4; 11-2018; 541-556
0022-3042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95825
identifier_str_mv Gallea, Jose Ignacio; Ambroggio, Ernesto Esteban; Vilcaes, Aldo Alejandro; James, Nicholas G.; Jameson, David M.; et al.; Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 147; 4; 11-2018; 541-556
0022-3042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/jnc.14573
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.14573
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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