Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization

Autores
Munafó, Juan Pablo; Fabiani, Camila; Maniscalchi, Athina del Valle; Salvador, Gabriela Alejandra; Peñalva, Daniel Alejandro; Antollini, Silvia Susana
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Cholesterol (Chol) is an essential lipid molecule critical for both the development and proper function of the nervous system. The adult brain contains over 20% of the body’s total Chol. In contrast to the distribution found in most mammalian cell membranes, approximately 85% of the Chol in synaptosomal membranes is located in the inner hemilayer, optimizing membrane rheology and supporting neuronal function. However, significant changes occur with aging, resulting in an increased proportion of Chol in the outer hemilayer. Conflicting hypotheses exist regarding how these changes affect β- amyloid (Aβ) aggregation, a hallmark of the Alzheimer's disease, and the precise mechanisms, particularly at low Aβ concentrations, remain unclear. To gain deeper insight into this process, lipid model membranes (large and giant unilamellar vesicles, LUVs and GUVs, respectively) composed of different lipids and Chol levels were employed. Several experimental techniques, including fluorescence spectroscopy, fluorescence microscopy, transmission electron microscopy, and dot blot were used to explore how the Chol membrane content and the resulting membrane biophysical status of the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases impact Aβ aggregation. A direct correlation between higher Chol membrane levels and an increase in Aβ aggregation over time was observed. In the presence of Aβ, high Chol levels were correlated with a marked increase in the membrane transition temperature (Tt) over time. By maintaining the same Chol level but changing other lipids, it was possible to conclude that, although Chol is essential for the initial stages of Aβ oligomerization, the biophysical state of the Ld-Lo coexistence is ultimately responsible for Aβ fibrillation. These findings may offer critical insights into the early molecular events of Alzheimer's disease, potentially advancing the understanding of its pathogenesis and opening new avenues for therapeutic intervention.
Fil: Munafó, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Fabiani, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Maniscalchi, Athina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Peñalva, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LI Reunión Anual de la Sociedad Argentina de Biofísica
Bahía Blanca
Argentina
Sociedad Argentina de Biofísica
Materia
CHOLESTEROL
BETA AMYLOID PEPTIDE
ALZHEIMER
MEMBRANE ORGANIZATION
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:11336/251743
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/251743
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network_name_str CONICET Digital (CONICET)
spelling Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane OrganizationMunafó, Juan PabloFabiani, CamilaManiscalchi, Athina del ValleSalvador, Gabriela AlejandraPeñalva, Daniel AlejandroAntollini, Silvia SusanaCHOLESTEROLBETA AMYLOID PEPTIDEALZHEIMERMEMBRANE ORGANIZATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cholesterol (Chol) is an essential lipid molecule critical for both the development and proper function of the nervous system. The adult brain contains over 20% of the body’s total Chol. In contrast to the distribution found in most mammalian cell membranes, approximately 85% of the Chol in synaptosomal membranes is located in the inner hemilayer, optimizing membrane rheology and supporting neuronal function. However, significant changes occur with aging, resulting in an increased proportion of Chol in the outer hemilayer. Conflicting hypotheses exist regarding how these changes affect β- amyloid (Aβ) aggregation, a hallmark of the Alzheimer's disease, and the precise mechanisms, particularly at low Aβ concentrations, remain unclear. To gain deeper insight into this process, lipid model membranes (large and giant unilamellar vesicles, LUVs and GUVs, respectively) composed of different lipids and Chol levels were employed. Several experimental techniques, including fluorescence spectroscopy, fluorescence microscopy, transmission electron microscopy, and dot blot were used to explore how the Chol membrane content and the resulting membrane biophysical status of the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases impact Aβ aggregation. A direct correlation between higher Chol membrane levels and an increase in Aβ aggregation over time was observed. In the presence of Aβ, high Chol levels were correlated with a marked increase in the membrane transition temperature (Tt) over time. By maintaining the same Chol level but changing other lipids, it was possible to conclude that, although Chol is essential for the initial stages of Aβ oligomerization, the biophysical state of the Ld-Lo coexistence is ultimately responsible for Aβ fibrillation. These findings may offer critical insights into the early molecular events of Alzheimer's disease, potentially advancing the understanding of its pathogenesis and opening new avenues for therapeutic intervention.Fil: Munafó, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Fabiani, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Maniscalchi, Athina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Peñalva, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLI Reunión Anual de la Sociedad Argentina de BiofísicaBahía BlancaArgentinaSociedad Argentina de BiofísicaSociedad Argentina de Biofísica2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/251743Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization; LI Reunión Anual de la Sociedad Argentina de Biofísica; Bahía Blanca; Argentina; 2024; 124-124CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/congreso-2024/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:14Zoai:ri.conicet.gov.ar:11336/251743instacron: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 09:46:14.895CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
title Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
spellingShingle Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
Munafó, Juan Pablo
CHOLESTEROL
BETA AMYLOID PEPTIDE
ALZHEIMER
MEMBRANE ORGANIZATION
title_short Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
title_full Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
title_fullStr Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
title_full_unstemmed Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
title_sort Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization
dc.creator.none.fl_str_mv Munafó, Juan Pablo
Fabiani, Camila
Maniscalchi, Athina del Valle
Salvador, Gabriela Alejandra
Peñalva, Daniel Alejandro
Antollini, Silvia Susana
author Munafó, Juan Pablo
author_facet Munafó, Juan Pablo
Fabiani, Camila
Maniscalchi, Athina del Valle
Salvador, Gabriela Alejandra
Peñalva, Daniel Alejandro
Antollini, Silvia Susana
author_role author
author2 Fabiani, Camila
Maniscalchi, Athina del Valle
Salvador, Gabriela Alejandra
Peñalva, Daniel Alejandro
Antollini, Silvia Susana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CHOLESTEROL
BETA AMYLOID PEPTIDE
ALZHEIMER
MEMBRANE ORGANIZATION
topic CHOLESTEROL
BETA AMYLOID PEPTIDE
ALZHEIMER
MEMBRANE ORGANIZATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cholesterol (Chol) is an essential lipid molecule critical for both the development and proper function of the nervous system. The adult brain contains over 20% of the body’s total Chol. In contrast to the distribution found in most mammalian cell membranes, approximately 85% of the Chol in synaptosomal membranes is located in the inner hemilayer, optimizing membrane rheology and supporting neuronal function. However, significant changes occur with aging, resulting in an increased proportion of Chol in the outer hemilayer. Conflicting hypotheses exist regarding how these changes affect β- amyloid (Aβ) aggregation, a hallmark of the Alzheimer's disease, and the precise mechanisms, particularly at low Aβ concentrations, remain unclear. To gain deeper insight into this process, lipid model membranes (large and giant unilamellar vesicles, LUVs and GUVs, respectively) composed of different lipids and Chol levels were employed. Several experimental techniques, including fluorescence spectroscopy, fluorescence microscopy, transmission electron microscopy, and dot blot were used to explore how the Chol membrane content and the resulting membrane biophysical status of the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases impact Aβ aggregation. A direct correlation between higher Chol membrane levels and an increase in Aβ aggregation over time was observed. In the presence of Aβ, high Chol levels were correlated with a marked increase in the membrane transition temperature (Tt) over time. By maintaining the same Chol level but changing other lipids, it was possible to conclude that, although Chol is essential for the initial stages of Aβ oligomerization, the biophysical state of the Ld-Lo coexistence is ultimately responsible for Aβ fibrillation. These findings may offer critical insights into the early molecular events of Alzheimer's disease, potentially advancing the understanding of its pathogenesis and opening new avenues for therapeutic intervention.
Fil: Munafó, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Fabiani, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Maniscalchi, Athina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Peñalva, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LI Reunión Anual de la Sociedad Argentina de Biofísica
Bahía Blanca
Argentina
Sociedad Argentina de Biofísica
description Cholesterol (Chol) is an essential lipid molecule critical for both the development and proper function of the nervous system. The adult brain contains over 20% of the body’s total Chol. In contrast to the distribution found in most mammalian cell membranes, approximately 85% of the Chol in synaptosomal membranes is located in the inner hemilayer, optimizing membrane rheology and supporting neuronal function. However, significant changes occur with aging, resulting in an increased proportion of Chol in the outer hemilayer. Conflicting hypotheses exist regarding how these changes affect β- amyloid (Aβ) aggregation, a hallmark of the Alzheimer's disease, and the precise mechanisms, particularly at low Aβ concentrations, remain unclear. To gain deeper insight into this process, lipid model membranes (large and giant unilamellar vesicles, LUVs and GUVs, respectively) composed of different lipids and Chol levels were employed. Several experimental techniques, including fluorescence spectroscopy, fluorescence microscopy, transmission electron microscopy, and dot blot were used to explore how the Chol membrane content and the resulting membrane biophysical status of the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases impact Aβ aggregation. A direct correlation between higher Chol membrane levels and an increase in Aβ aggregation over time was observed. In the presence of Aβ, high Chol levels were correlated with a marked increase in the membrane transition temperature (Tt) over time. By maintaining the same Chol level but changing other lipids, it was possible to conclude that, although Chol is essential for the initial stages of Aβ oligomerization, the biophysical state of the Ld-Lo coexistence is ultimately responsible for Aβ fibrillation. These findings may offer critical insights into the early molecular events of Alzheimer's disease, potentially advancing the understanding of its pathogenesis and opening new avenues for therapeutic intervention.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/251743
Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization; LI Reunión Anual de la Sociedad Argentina de Biofísica; Bahía Blanca; Argentina; 2024; 124-124
CONICET Digital
CONICET
url http://hdl.handle.net/11336/251743
identifier_str_mv Key Drivers of Beta-Amyloid Peptide Aggregation: Cholesterol Content and Membrane Organization; LI Reunión Anual de la Sociedad Argentina de Biofísica; Bahía Blanca; Argentina; 2024; 124-124
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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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
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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