Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase

Autores
Peñalva, Daniel Alejandro; Munafó, Juan Pablo; Oresti, Gerardo Martin; Antollini, Silvia Susana
Año de publicación
2025
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Alzheimer’s disease (AD) involves a progressive deterioration of neuronal connectivity and synaptic function, driven by multiple interrelated pathological mechanisms. Among these, the aberrant aggregation of β-amyloid (Aβ) peptides and the decline of cholinergic transmission represent two converging hallmarks. Beyond its catalytic role in acetylcholine hydrolysis, acetylcholinesterase (AChE) can also promote Aβ assembly through peripheral binding interactions, thereby amplifying neurotoxic effects. Increasing evidence highlights the critical influence of membrane lipid composition, particularly cholesterol (chol), in modulating these processes. Changes with aging and Alzheimer’s risk factors in chol distribution across membrane leaflets promote lipid environments that enhance Aβ–membrane interactions and facilitate peptide aggregation. Building upon our previous studies in which model membranes with defined chol levels were shown to influence Aβ aggregation, the present work investigates how natural fatty acids (FA) affect peptide aggregation in chol-enriched systems. Using a combination of fluorescence spectroscopy, microscopy, and molecular docking, we evaluated the ability of various FA to inhibit AChE activity and additionally prevent Aβ aggregation. Notably, oleic acid and docosahexaenoic acid (DHA) exhibited the strongest capacity to interfere with Aβ aggregation and AChE catalytic activity, consistent with their predicted interactions at the catalytic anionic site revealed by molecular docking. These effects showed a clear dependence on FA chain length and degree of unsaturation. These findings indicate that specific unsaturated FA modulate membrane topology and alter the lateral distribution of chol, thereby attenuating the membrane-mediated enhancement of Aβ oligomerization and fibrillation, while also targeting AChE activity. Altogether, our results support the potential of FA-based molecules as multifunctional therapeutic candidates for AD.
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: 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
Fil: Oresti, Gerardo Martin. 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
LIII Reunión Anual de la Sociedad Argentina de Biofísica
Buenos Aires
Argentina
Sociedad Argentina de Biofísica
Materia
ALZHEIMER'S DISEASE
β-AMYLOID
ACETYLCHOLINESTERASE
CHOLESTEROL
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:11336/279649
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/279649
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and AcetylcholinesterasePeñalva, Daniel AlejandroMunafó, Juan PabloOresti, Gerardo MartinAntollini, Silvia SusanaALZHEIMER'S DISEASEβ-AMYLOIDACETYLCHOLINESTERASECHOLESTEROLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alzheimer’s disease (AD) involves a progressive deterioration of neuronal connectivity and synaptic function, driven by multiple interrelated pathological mechanisms. Among these, the aberrant aggregation of β-amyloid (Aβ) peptides and the decline of cholinergic transmission represent two converging hallmarks. Beyond its catalytic role in acetylcholine hydrolysis, acetylcholinesterase (AChE) can also promote Aβ assembly through peripheral binding interactions, thereby amplifying neurotoxic effects. Increasing evidence highlights the critical influence of membrane lipid composition, particularly cholesterol (chol), in modulating these processes. Changes with aging and Alzheimer’s risk factors in chol distribution across membrane leaflets promote lipid environments that enhance Aβ–membrane interactions and facilitate peptide aggregation. Building upon our previous studies in which model membranes with defined chol levels were shown to influence Aβ aggregation, the present work investigates how natural fatty acids (FA) affect peptide aggregation in chol-enriched systems. Using a combination of fluorescence spectroscopy, microscopy, and molecular docking, we evaluated the ability of various FA to inhibit AChE activity and additionally prevent Aβ aggregation. Notably, oleic acid and docosahexaenoic acid (DHA) exhibited the strongest capacity to interfere with Aβ aggregation and AChE catalytic activity, consistent with their predicted interactions at the catalytic anionic site revealed by molecular docking. These effects showed a clear dependence on FA chain length and degree of unsaturation. These findings indicate that specific unsaturated FA modulate membrane topology and alter the lateral distribution of chol, thereby attenuating the membrane-mediated enhancement of Aβ oligomerization and fibrillation, while also targeting AChE activity. Altogether, our results support the potential of FA-based molecules as multifunctional therapeutic candidates for AD.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; ArgentinaFil: 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; ArgentinaFil: Oresti, Gerardo Martin. 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; ArgentinaLIII Reunión Anual de la Sociedad Argentina de BiofísicaBuenos AiresArgentinaSociedad Argentina de BiofísicaSociedad Argentina de BiofísicaVázquez, Diego EduardoDi Lella, Santiago2025info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/279649Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase; LIII Reunión Anual de la Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2025; 97-97978-987-48938-3-3CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/congreso-2025/#resumenesNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:05:17Zoai:ri.conicet.gov.ar:11336/279649instacron: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:34982026-02-26 10:05:17.456CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
title Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
spellingShingle Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
Peñalva, Daniel Alejandro
ALZHEIMER'S DISEASE
β-AMYLOID
ACETYLCHOLINESTERASE
CHOLESTEROL
title_short Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
title_full Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
title_fullStr Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
title_full_unstemmed Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
title_sort Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase
dc.creator.none.fl_str_mv Peñalva, Daniel Alejandro
Munafó, Juan Pablo
Oresti, Gerardo Martin
Antollini, Silvia Susana
author Peñalva, Daniel Alejandro
author_facet Peñalva, Daniel Alejandro
Munafó, Juan Pablo
Oresti, Gerardo Martin
Antollini, Silvia Susana
author_role author
author2 Munafó, Juan Pablo
Oresti, Gerardo Martin
Antollini, Silvia Susana
author2_role author
author
author
dc.contributor.none.fl_str_mv Vázquez, Diego Eduardo
Di Lella, Santiago
dc.subject.none.fl_str_mv ALZHEIMER'S DISEASE
β-AMYLOID
ACETYLCHOLINESTERASE
CHOLESTEROL
topic ALZHEIMER'S DISEASE
β-AMYLOID
ACETYLCHOLINESTERASE
CHOLESTEROL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alzheimer’s disease (AD) involves a progressive deterioration of neuronal connectivity and synaptic function, driven by multiple interrelated pathological mechanisms. Among these, the aberrant aggregation of β-amyloid (Aβ) peptides and the decline of cholinergic transmission represent two converging hallmarks. Beyond its catalytic role in acetylcholine hydrolysis, acetylcholinesterase (AChE) can also promote Aβ assembly through peripheral binding interactions, thereby amplifying neurotoxic effects. Increasing evidence highlights the critical influence of membrane lipid composition, particularly cholesterol (chol), in modulating these processes. Changes with aging and Alzheimer’s risk factors in chol distribution across membrane leaflets promote lipid environments that enhance Aβ–membrane interactions and facilitate peptide aggregation. Building upon our previous studies in which model membranes with defined chol levels were shown to influence Aβ aggregation, the present work investigates how natural fatty acids (FA) affect peptide aggregation in chol-enriched systems. Using a combination of fluorescence spectroscopy, microscopy, and molecular docking, we evaluated the ability of various FA to inhibit AChE activity and additionally prevent Aβ aggregation. Notably, oleic acid and docosahexaenoic acid (DHA) exhibited the strongest capacity to interfere with Aβ aggregation and AChE catalytic activity, consistent with their predicted interactions at the catalytic anionic site revealed by molecular docking. These effects showed a clear dependence on FA chain length and degree of unsaturation. These findings indicate that specific unsaturated FA modulate membrane topology and alter the lateral distribution of chol, thereby attenuating the membrane-mediated enhancement of Aβ oligomerization and fibrillation, while also targeting AChE activity. Altogether, our results support the potential of FA-based molecules as multifunctional therapeutic candidates for AD.
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: 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
Fil: Oresti, Gerardo Martin. 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
LIII Reunión Anual de la Sociedad Argentina de Biofísica
Buenos Aires
Argentina
Sociedad Argentina de Biofísica
description Alzheimer’s disease (AD) involves a progressive deterioration of neuronal connectivity and synaptic function, driven by multiple interrelated pathological mechanisms. Among these, the aberrant aggregation of β-amyloid (Aβ) peptides and the decline of cholinergic transmission represent two converging hallmarks. Beyond its catalytic role in acetylcholine hydrolysis, acetylcholinesterase (AChE) can also promote Aβ assembly through peripheral binding interactions, thereby amplifying neurotoxic effects. Increasing evidence highlights the critical influence of membrane lipid composition, particularly cholesterol (chol), in modulating these processes. Changes with aging and Alzheimer’s risk factors in chol distribution across membrane leaflets promote lipid environments that enhance Aβ–membrane interactions and facilitate peptide aggregation. Building upon our previous studies in which model membranes with defined chol levels were shown to influence Aβ aggregation, the present work investigates how natural fatty acids (FA) affect peptide aggregation in chol-enriched systems. Using a combination of fluorescence spectroscopy, microscopy, and molecular docking, we evaluated the ability of various FA to inhibit AChE activity and additionally prevent Aβ aggregation. Notably, oleic acid and docosahexaenoic acid (DHA) exhibited the strongest capacity to interfere with Aβ aggregation and AChE catalytic activity, consistent with their predicted interactions at the catalytic anionic site revealed by molecular docking. These effects showed a clear dependence on FA chain length and degree of unsaturation. These findings indicate that specific unsaturated FA modulate membrane topology and alter the lateral distribution of chol, thereby attenuating the membrane-mediated enhancement of Aβ oligomerization and fibrillation, while also targeting AChE activity. Altogether, our results support the potential of FA-based molecules as multifunctional therapeutic candidates for AD.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
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/11336/279649
Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase; LIII Reunión Anual de la Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2025; 97-97
978-987-48938-3-3
CONICET Digital
CONICET
url http://hdl.handle.net/11336/279649
identifier_str_mv Impact of Unsaturated Fatty Acids on β-Amyloid Aggregation Mediated by Cholesterol-Rich Membranes and Acetylcholinesterase; LIII Reunión Anual de la Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2025; 97-97
978-987-48938-3-3
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/congreso-2025/#resumenes
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
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)
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 13.176822

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