-α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration

Autores
Alza, Natalia Paola; Conde, Melisa Ailén; Salvador, Gabriela Alejandra
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Pathological accumulation of α-synuclein (α-syn) is a hallmark of Parkinson ‘s disease. α-syn is highly expressed in the brain and has the intriguing characteristic of interacting with lipids. However, little is known about its biological role. We demonstrated that α-syn overexpression downregulates neurofilament expression (NF) through the modulation of phosphatidic acid signaling (Conde et al, 2018). Here, we studied lipid metabolism in neuroblastoma cells either stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-WT-α-syn (WT α-syn). WT α-syn neurons displayed an increase in triacylglycerides (TAG) and cholesterol content consequently with lipid droplet (LD) accumulation. α-syn overexpression also triggered SREBP-2 nuclear translocation coincidently with this lipid metabolic switch. Enhancers of α-syn aggregation (iron, manganese and bortezomib) increased LD content. WT α-syn overexpression also induced Acyl-CoA synthetase activation which explained, at least in part, the increase in TAG, a rather unusual occurrence in healthy neurons. Pharmacological inhibition of TAG synthesis turned the neurons more vulnerable to the presence of WT α-syn. Additionally, NF recovery increased the expression of cleaved caspase 3. In conclusion, α-syn modulates neuronal lipid biology together with the loss of NF as part of a neuroprotective strategy.
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 Biología, Bioquímica y Farmacia; 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: 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
XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias
Cordoba
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
ALPHA-SYNUCLEIN
LIPID DROPLETS
LIPID METABOLISM
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:11336/161834
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/161834
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegenerationAlza, Natalia PaolaConde, Melisa AilénSalvador, Gabriela AlejandraALPHA-SYNUCLEINLIPID DROPLETSLIPID METABOLISMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Pathological accumulation of α-synuclein (α-syn) is a hallmark of Parkinson ‘s disease. α-syn is highly expressed in the brain and has the intriguing characteristic of interacting with lipids. However, little is known about its biological role. We demonstrated that α-syn overexpression downregulates neurofilament expression (NF) through the modulation of phosphatidic acid signaling (Conde et al, 2018). Here, we studied lipid metabolism in neuroblastoma cells either stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-WT-α-syn (WT α-syn). WT α-syn neurons displayed an increase in triacylglycerides (TAG) and cholesterol content consequently with lipid droplet (LD) accumulation. α-syn overexpression also triggered SREBP-2 nuclear translocation coincidently with this lipid metabolic switch. Enhancers of α-syn aggregation (iron, manganese and bortezomib) increased LD content. WT α-syn overexpression also induced Acyl-CoA synthetase activation which explained, at least in part, the increase in TAG, a rather unusual occurrence in healthy neurons. Pharmacological inhibition of TAG synthesis turned the neurons more vulnerable to the presence of WT α-syn. Additionally, NF recovery increased the expression of cleaved caspase 3. In conclusion, α-syn modulates neuronal lipid biology together with the loss of NF as part of a neuroprotective strategy.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 Biología, Bioquímica y Farmacia; 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: 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; ArgentinaXXXIII Congreso Anual de la Sociedad Argentina de Investigación en NeurocienciasCordobaArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/161834-α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Cordoba; Argentina; 2018; 179-179CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/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 Técnicas2025-09-03T09:54:52Zoai:ri.conicet.gov.ar:11336/161834instacron: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 09:54:53.19CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
title -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
spellingShingle -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
Alza, Natalia Paola
ALPHA-SYNUCLEIN
LIPID DROPLETS
LIPID METABOLISM
title_short -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
title_full -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
title_fullStr -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
title_full_unstemmed -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
title_sort -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration
dc.creator.none.fl_str_mv Alza, Natalia Paola
Conde, Melisa Ailén
Salvador, Gabriela Alejandra
author Alza, Natalia Paola
author_facet Alza, Natalia Paola
Conde, Melisa Ailén
Salvador, Gabriela Alejandra
author_role author
author2 Conde, Melisa Ailén
Salvador, Gabriela Alejandra
author2_role author
author
dc.subject.none.fl_str_mv ALPHA-SYNUCLEIN
LIPID DROPLETS
LIPID METABOLISM
topic ALPHA-SYNUCLEIN
LIPID DROPLETS
LIPID METABOLISM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Pathological accumulation of α-synuclein (α-syn) is a hallmark of Parkinson ‘s disease. α-syn is highly expressed in the brain and has the intriguing characteristic of interacting with lipids. However, little is known about its biological role. We demonstrated that α-syn overexpression downregulates neurofilament expression (NF) through the modulation of phosphatidic acid signaling (Conde et al, 2018). Here, we studied lipid metabolism in neuroblastoma cells either stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-WT-α-syn (WT α-syn). WT α-syn neurons displayed an increase in triacylglycerides (TAG) and cholesterol content consequently with lipid droplet (LD) accumulation. α-syn overexpression also triggered SREBP-2 nuclear translocation coincidently with this lipid metabolic switch. Enhancers of α-syn aggregation (iron, manganese and bortezomib) increased LD content. WT α-syn overexpression also induced Acyl-CoA synthetase activation which explained, at least in part, the increase in TAG, a rather unusual occurrence in healthy neurons. Pharmacological inhibition of TAG synthesis turned the neurons more vulnerable to the presence of WT α-syn. Additionally, NF recovery increased the expression of cleaved caspase 3. In conclusion, α-syn modulates neuronal lipid biology together with the loss of NF as part of a neuroprotective strategy.
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 Biología, Bioquímica y Farmacia; 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: 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
XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias
Cordoba
Argentina
Sociedad Argentina de Investigación en Neurociencias
description Pathological accumulation of α-synuclein (α-syn) is a hallmark of Parkinson ‘s disease. α-syn is highly expressed in the brain and has the intriguing characteristic of interacting with lipids. However, little is known about its biological role. We demonstrated that α-syn overexpression downregulates neurofilament expression (NF) through the modulation of phosphatidic acid signaling (Conde et al, 2018). Here, we studied lipid metabolism in neuroblastoma cells either stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-WT-α-syn (WT α-syn). WT α-syn neurons displayed an increase in triacylglycerides (TAG) and cholesterol content consequently with lipid droplet (LD) accumulation. α-syn overexpression also triggered SREBP-2 nuclear translocation coincidently with this lipid metabolic switch. Enhancers of α-syn aggregation (iron, manganese and bortezomib) increased LD content. WT α-syn overexpression also induced Acyl-CoA synthetase activation which explained, at least in part, the increase in TAG, a rather unusual occurrence in healthy neurons. Pharmacological inhibition of TAG synthesis turned the neurons more vulnerable to the presence of WT α-syn. Additionally, NF recovery increased the expression of cleaved caspase 3. In conclusion, α-syn modulates neuronal lipid biology together with the loss of NF as part of a neuroprotective strategy.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/11336/161834
-α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Cordoba; Argentina; 2018; 179-179
CONICET Digital
CONICET
url http://hdl.handle.net/11336/161834
identifier_str_mv -α-synuclein overexpression triggers a lipid metabolic switch: lipid droplets as an early marker of neurodegeneration; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Cordoba; Argentina; 2018; 179-179
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://saneurociencias.org.ar/congresos-san-2/
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
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
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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