α-Synuclein and lipid metabolism: intersecting pathways

Autores
Alza, Natalia Paola; Conde, Melisa Ailén; Scodelaro Bilbao, Paola Gabriela; González Pardo, Verónica; Salvador, Gabriela Alejandra
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
α-synuclein (α-syn) aggregation and fibrillation is a hallmark of a class of neurodegenerative disorders known as synucleinopathies. An intriguing and not completely clarified feature of α-syn is the many ways in which it interacts with lipids. In the present study, we aimed to investigate the effect of α-syn overexpression on neuronal lipid metabolism. For this purpose, human IMR-32 neuroblastoma cells stably transfected with either pcDNA3 vector (control) or pcDNA3-WT-α-syn (WT α-syn) were used. We observed that α-syn overexpression induced the accumulation of cytosolic lipid droplets (LD) and cholesterol (Chol) in lysosomes. LD increase was coincident with a rise in triacylglycerol (TAG) and Chol esters content. To ascertain the mechanism involved in LD accumulation, pharmacological inhibitors of proteasomal degradation and autophagy were used. Whereas autophagy inhibition did not affect neutral lipids content, the blockage of proteasomal degradation was able to increase LD accumulation in WT α-syn cells. In silico analysis performed with MyProteinNet server (Yeger-Lotem lab) postulates a positive correlation between α-syn and sterol regulatory element-binding gen (SREBF-2). To corroborate these data in our experimental model, we evaluated the status of the transcription factors SREBP-1 and SREBP-2. SREBP-1 nuclear localization was slightly diminished by α-syn overexpression with decreased levels of fatty acid synthase protein expression. In contrast, α-syn overexpression promoted SREBP-2 nuclear translocation, with no increment in the expression levels of the downstream genes related to Chol synthesis. Intriguingly, fatty acid Coenzyme A esterification and acylation into Chol and diacylglycerides were increased in WT α-syn cells. To elucidate the source of fatty acids availability, we measured phospholipid content and TAG hydrolysis. WT α-syn cells displayed diminished levels of cardiolipin and phosphatidic acid with no changes in TAG hydrolysis. Our results allow us to conclude that: α-syn overexpression induces a metabolic switch that triggers the neuronal accumulation of neutral lipids by activating several mechanisms: (i) increased phospholipid hydrolysis, (ii) a rise in fatty acids esterification into Chol and diacylglycerols, and (iii) Chol accumulation in lysosomes probably due to an increment in its uptake.
Fil: Alza, Natalia Paola. 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 Química; Argentina
Fil: Conde, Melisa Ailén. 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: Scodelaro Bilbao, Paola Gabriela. 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: González Pardo, Verónica. Universidad Nacional del Sur. Departamento de Química; 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
The LV Annual SAIB Meeting and XIV PABMB Congress
Salta
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
Materia
SYNUCLEINOPATHIES
LIPID DROPLETS
LIPIDS
SYNUCLEIN
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:11336/157730
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling α-Synuclein and lipid metabolism: intersecting pathwaysAlza, Natalia PaolaConde, Melisa AilénScodelaro Bilbao, Paola GabrielaGonzález Pardo, VerónicaSalvador, Gabriela AlejandraSYNUCLEINOPATHIESLIPID DROPLETSLIPIDSSYNUCLEINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1α-synuclein (α-syn) aggregation and fibrillation is a hallmark of a class of neurodegenerative disorders known as synucleinopathies. An intriguing and not completely clarified feature of α-syn is the many ways in which it interacts with lipids. In the present study, we aimed to investigate the effect of α-syn overexpression on neuronal lipid metabolism. For this purpose, human IMR-32 neuroblastoma cells stably transfected with either pcDNA3 vector (control) or pcDNA3-WT-α-syn (WT α-syn) were used. We observed that α-syn overexpression induced the accumulation of cytosolic lipid droplets (LD) and cholesterol (Chol) in lysosomes. LD increase was coincident with a rise in triacylglycerol (TAG) and Chol esters content. To ascertain the mechanism involved in LD accumulation, pharmacological inhibitors of proteasomal degradation and autophagy were used. Whereas autophagy inhibition did not affect neutral lipids content, the blockage of proteasomal degradation was able to increase LD accumulation in WT α-syn cells. In silico analysis performed with MyProteinNet server (Yeger-Lotem lab) postulates a positive correlation between α-syn and sterol regulatory element-binding gen (SREBF-2). To corroborate these data in our experimental model, we evaluated the status of the transcription factors SREBP-1 and SREBP-2. SREBP-1 nuclear localization was slightly diminished by α-syn overexpression with decreased levels of fatty acid synthase protein expression. In contrast, α-syn overexpression promoted SREBP-2 nuclear translocation, with no increment in the expression levels of the downstream genes related to Chol synthesis. Intriguingly, fatty acid Coenzyme A esterification and acylation into Chol and diacylglycerides were increased in WT α-syn cells. To elucidate the source of fatty acids availability, we measured phospholipid content and TAG hydrolysis. WT α-syn cells displayed diminished levels of cardiolipin and phosphatidic acid with no changes in TAG hydrolysis. Our results allow us to conclude that: α-syn overexpression induces a metabolic switch that triggers the neuronal accumulation of neutral lipids by activating several mechanisms: (i) increased phospholipid hydrolysis, (ii) a rise in fatty acids esterification into Chol and diacylglycerols, and (iii) Chol accumulation in lysosomes probably due to an increment in its uptake.Fil: Alza, Natalia Paola. 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 Química; ArgentinaFil: Conde, Melisa Ailén. 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: Scodelaro Bilbao, Paola Gabriela. 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: González Pardo, Verónica. Universidad Nacional del Sur. Departamento de Química; 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; ArgentinaThe LV Annual SAIB Meeting and XIV PABMB CongressSaltaArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularTech Science Press2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/157730α-Synuclein and lipid metabolism: intersecting pathways; The LV Annual SAIB Meeting and XIV PABMB Congress; Salta; Argentina; 2019; 1-61667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/info:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/index.php?q=node/562Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:59:19Zoai:ri.conicet.gov.ar:11336/157730instacron: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:34982025-10-15 14:59:19.355CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv α-Synuclein and lipid metabolism: intersecting pathways
title α-Synuclein and lipid metabolism: intersecting pathways
spellingShingle α-Synuclein and lipid metabolism: intersecting pathways
Alza, Natalia Paola
SYNUCLEINOPATHIES
LIPID DROPLETS
LIPIDS
SYNUCLEIN
title_short α-Synuclein and lipid metabolism: intersecting pathways
title_full α-Synuclein and lipid metabolism: intersecting pathways
title_fullStr α-Synuclein and lipid metabolism: intersecting pathways
title_full_unstemmed α-Synuclein and lipid metabolism: intersecting pathways
title_sort α-Synuclein and lipid metabolism: intersecting pathways
dc.creator.none.fl_str_mv Alza, Natalia Paola
Conde, Melisa Ailén
Scodelaro Bilbao, Paola Gabriela
González Pardo, Verónica
Salvador, Gabriela Alejandra
author Alza, Natalia Paola
author_facet Alza, Natalia Paola
Conde, Melisa Ailén
Scodelaro Bilbao, Paola Gabriela
González Pardo, Verónica
Salvador, Gabriela Alejandra
author_role author
author2 Conde, Melisa Ailén
Scodelaro Bilbao, Paola Gabriela
González Pardo, Verónica
Salvador, Gabriela Alejandra
author2_role author
author
author
author
dc.subject.none.fl_str_mv SYNUCLEINOPATHIES
LIPID DROPLETS
LIPIDS
SYNUCLEIN
topic SYNUCLEINOPATHIES
LIPID DROPLETS
LIPIDS
SYNUCLEIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv α-synuclein (α-syn) aggregation and fibrillation is a hallmark of a class of neurodegenerative disorders known as synucleinopathies. An intriguing and not completely clarified feature of α-syn is the many ways in which it interacts with lipids. In the present study, we aimed to investigate the effect of α-syn overexpression on neuronal lipid metabolism. For this purpose, human IMR-32 neuroblastoma cells stably transfected with either pcDNA3 vector (control) or pcDNA3-WT-α-syn (WT α-syn) were used. We observed that α-syn overexpression induced the accumulation of cytosolic lipid droplets (LD) and cholesterol (Chol) in lysosomes. LD increase was coincident with a rise in triacylglycerol (TAG) and Chol esters content. To ascertain the mechanism involved in LD accumulation, pharmacological inhibitors of proteasomal degradation and autophagy were used. Whereas autophagy inhibition did not affect neutral lipids content, the blockage of proteasomal degradation was able to increase LD accumulation in WT α-syn cells. In silico analysis performed with MyProteinNet server (Yeger-Lotem lab) postulates a positive correlation between α-syn and sterol regulatory element-binding gen (SREBF-2). To corroborate these data in our experimental model, we evaluated the status of the transcription factors SREBP-1 and SREBP-2. SREBP-1 nuclear localization was slightly diminished by α-syn overexpression with decreased levels of fatty acid synthase protein expression. In contrast, α-syn overexpression promoted SREBP-2 nuclear translocation, with no increment in the expression levels of the downstream genes related to Chol synthesis. Intriguingly, fatty acid Coenzyme A esterification and acylation into Chol and diacylglycerides were increased in WT α-syn cells. To elucidate the source of fatty acids availability, we measured phospholipid content and TAG hydrolysis. WT α-syn cells displayed diminished levels of cardiolipin and phosphatidic acid with no changes in TAG hydrolysis. Our results allow us to conclude that: α-syn overexpression induces a metabolic switch that triggers the neuronal accumulation of neutral lipids by activating several mechanisms: (i) increased phospholipid hydrolysis, (ii) a rise in fatty acids esterification into Chol and diacylglycerols, and (iii) Chol accumulation in lysosomes probably due to an increment in its uptake.
Fil: Alza, Natalia Paola. 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 Química; Argentina
Fil: Conde, Melisa Ailén. 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: Scodelaro Bilbao, Paola Gabriela. 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: González Pardo, Verónica. Universidad Nacional del Sur. Departamento de Química; 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
The LV Annual SAIB Meeting and XIV PABMB Congress
Salta
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
description α-synuclein (α-syn) aggregation and fibrillation is a hallmark of a class of neurodegenerative disorders known as synucleinopathies. An intriguing and not completely clarified feature of α-syn is the many ways in which it interacts with lipids. In the present study, we aimed to investigate the effect of α-syn overexpression on neuronal lipid metabolism. For this purpose, human IMR-32 neuroblastoma cells stably transfected with either pcDNA3 vector (control) or pcDNA3-WT-α-syn (WT α-syn) were used. We observed that α-syn overexpression induced the accumulation of cytosolic lipid droplets (LD) and cholesterol (Chol) in lysosomes. LD increase was coincident with a rise in triacylglycerol (TAG) and Chol esters content. To ascertain the mechanism involved in LD accumulation, pharmacological inhibitors of proteasomal degradation and autophagy were used. Whereas autophagy inhibition did not affect neutral lipids content, the blockage of proteasomal degradation was able to increase LD accumulation in WT α-syn cells. In silico analysis performed with MyProteinNet server (Yeger-Lotem lab) postulates a positive correlation between α-syn and sterol regulatory element-binding gen (SREBF-2). To corroborate these data in our experimental model, we evaluated the status of the transcription factors SREBP-1 and SREBP-2. SREBP-1 nuclear localization was slightly diminished by α-syn overexpression with decreased levels of fatty acid synthase protein expression. In contrast, α-syn overexpression promoted SREBP-2 nuclear translocation, with no increment in the expression levels of the downstream genes related to Chol synthesis. Intriguingly, fatty acid Coenzyme A esterification and acylation into Chol and diacylglycerides were increased in WT α-syn cells. To elucidate the source of fatty acids availability, we measured phospholipid content and TAG hydrolysis. WT α-syn cells displayed diminished levels of cardiolipin and phosphatidic acid with no changes in TAG hydrolysis. Our results allow us to conclude that: α-syn overexpression induces a metabolic switch that triggers the neuronal accumulation of neutral lipids by activating several mechanisms: (i) increased phospholipid hydrolysis, (ii) a rise in fatty acids esterification into Chol and diacylglycerols, and (iii) Chol accumulation in lysosomes probably due to an increment in its uptake.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
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/11336/157730
α-Synuclein and lipid metabolism: intersecting pathways; The LV Annual SAIB Meeting and XIV PABMB Congress; Salta; Argentina; 2019; 1-6
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/157730
identifier_str_mv α-Synuclein and lipid metabolism: intersecting pathways; The LV Annual SAIB Meeting and XIV PABMB Congress; Salta; Argentina; 2019; 1-6
1667-5746
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/index.php?q=node/562
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 Tech Science Press
publisher.none.fl_str_mv Tech Science Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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