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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/157730
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:03:05Zoai: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:34982025-09-29 10:03:05.616CONICET 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 |
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2019 |
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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 |
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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 |
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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 |
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eng |
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eng |
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Tech Science Press |
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Tech Science Press |
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