Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies

Autores
Alza, Natalia Paola; Conde, Melisa Ailén; Maniscalchi, Athina del Valle; Benzi Juncos, Oriana Nicole; Funk, Melania Iara; Salvador, Gabriela A.
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Alpha-synuclein (aSyn) pathology is a hallmark in the onset and progression of several synucleinopathies, including Parkinson’s disease. It has been demonstrated that lipid disturbances are associated with aSyn pathology. Our aim was to study neutral lipid metabolism in several in vivo and in vitro models of aSyn accumulation. To this end, different forms of aSyn overexpressed in neurons and toxicant-induced animal models related with synucleinopathies were used. In neuronal cultures, we demonstrated that the overexpression of aSyn (WT and mutant A53T) induced the accumulation of lipid droplets (LD) and free cholesterol (p<0.01). We found that LD biogenesis is a “hormesis mechanism” for preventing neuronal death induced by proteostasis impairment. Neuron-glia crosstalk was evaluated using neuronal secretomes, demonstrating that WT and A53T neurons exacerbated LD accumulation in glial cells. Moreover, the pesticide maneb triggered ferroptosis associated with aSyn overexpression in neurons with a rise in neutral lipid content (p<0.05). These results suggest that altered lipidostasis could be a hallmark of early aSyn-induced neurodegeneration. Mice exposed to neurotoxicants, as maneb and iron overload, showed aSyn upregulation (p<0.05) in whole brain and midbrain associated with motor impairment. In addition, the loss of tyrosine hydroxylase neurons in midbrain (p<0.001) was related to ferroptosis markers. Midbrain lipid profiles revealed that injured mice presented lipolysis as a consequence of diminished neutral lipid acylation (p<0.01) and lipogenesis, and higher cholesteryl ester deacylation rendering cholesterol accumulation (p<0.05). Neuronal death and movement disorders are linked with active lipolysis in in vivo models. Thus, indicating that marked injury in synucleinopathies is accompanied by impaired LD formation with cholesterol accumulation. Taken together, our results postulate LD as ying/yang markers of different stages of aSyn-induced neurodegeneration
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: 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
Fil: Benzi Juncos, Oriana Nicole. 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: Funk, Melania Iara. 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: Salvador, Gabriela A.. 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
Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
SYNUCLEINOPATHIES
LIPID DROPLETS
NEURODEGENERATION
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:11336/228689
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathiesAlza, Natalia PaolaConde, Melisa AilénManiscalchi, Athina del ValleBenzi Juncos, Oriana NicoleFunk, Melania IaraSalvador, Gabriela A.SYNUCLEINOPATHIESLIPID DROPLETSNEURODEGENERATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alpha-synuclein (aSyn) pathology is a hallmark in the onset and progression of several synucleinopathies, including Parkinson’s disease. It has been demonstrated that lipid disturbances are associated with aSyn pathology. Our aim was to study neutral lipid metabolism in several in vivo and in vitro models of aSyn accumulation. To this end, different forms of aSyn overexpressed in neurons and toxicant-induced animal models related with synucleinopathies were used. In neuronal cultures, we demonstrated that the overexpression of aSyn (WT and mutant A53T) induced the accumulation of lipid droplets (LD) and free cholesterol (p<0.01). We found that LD biogenesis is a “hormesis mechanism” for preventing neuronal death induced by proteostasis impairment. Neuron-glia crosstalk was evaluated using neuronal secretomes, demonstrating that WT and A53T neurons exacerbated LD accumulation in glial cells. Moreover, the pesticide maneb triggered ferroptosis associated with aSyn overexpression in neurons with a rise in neutral lipid content (p<0.05). These results suggest that altered lipidostasis could be a hallmark of early aSyn-induced neurodegeneration. Mice exposed to neurotoxicants, as maneb and iron overload, showed aSyn upregulation (p<0.05) in whole brain and midbrain associated with motor impairment. In addition, the loss of tyrosine hydroxylase neurons in midbrain (p<0.001) was related to ferroptosis markers. Midbrain lipid profiles revealed that injured mice presented lipolysis as a consequence of diminished neutral lipid acylation (p<0.01) and lipogenesis, and higher cholesteryl ester deacylation rendering cholesterol accumulation (p<0.05). Neuronal death and movement disorders are linked with active lipolysis in in vivo models. Thus, indicating that marked injury in synucleinopathies is accompanied by impaired LD formation with cholesterol accumulation. Taken together, our results postulate LD as ying/yang markers of different stages of aSyn-induced neurodegenerationFil: 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: 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; ArgentinaFil: Benzi Juncos, Oriana Nicole. 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: Funk, Melania Iara. 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: Salvador, Gabriela A.. 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; ArgentinaReunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)Mar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de BiologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista MedicinaLuthy, Isabel AliciaPerez Martinez, Silvina LauraSimonovich, VenturaPinto, Gabriel2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228689Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies; Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL); Mar del Plata; Argentina; 2023; 70-700025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:17Zoai:ri.conicet.gov.ar:11336/228689instacron: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 10:11:17.986CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
title Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
spellingShingle Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
Alza, Natalia Paola
SYNUCLEINOPATHIES
LIPID DROPLETS
NEURODEGENERATION
title_short Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
title_full Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
title_fullStr Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
title_full_unstemmed Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
title_sort Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies
dc.creator.none.fl_str_mv Alza, Natalia Paola
Conde, Melisa Ailén
Maniscalchi, Athina del Valle
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Salvador, Gabriela A.
author Alza, Natalia Paola
author_facet Alza, Natalia Paola
Conde, Melisa Ailén
Maniscalchi, Athina del Valle
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Salvador, Gabriela A.
author_role author
author2 Conde, Melisa Ailén
Maniscalchi, Athina del Valle
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Salvador, Gabriela A.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Luthy, Isabel Alicia
Perez Martinez, Silvina Laura
Simonovich, Ventura
Pinto, Gabriel
dc.subject.none.fl_str_mv SYNUCLEINOPATHIES
LIPID DROPLETS
NEURODEGENERATION
topic SYNUCLEINOPATHIES
LIPID DROPLETS
NEURODEGENERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alpha-synuclein (aSyn) pathology is a hallmark in the onset and progression of several synucleinopathies, including Parkinson’s disease. It has been demonstrated that lipid disturbances are associated with aSyn pathology. Our aim was to study neutral lipid metabolism in several in vivo and in vitro models of aSyn accumulation. To this end, different forms of aSyn overexpressed in neurons and toxicant-induced animal models related with synucleinopathies were used. In neuronal cultures, we demonstrated that the overexpression of aSyn (WT and mutant A53T) induced the accumulation of lipid droplets (LD) and free cholesterol (p<0.01). We found that LD biogenesis is a “hormesis mechanism” for preventing neuronal death induced by proteostasis impairment. Neuron-glia crosstalk was evaluated using neuronal secretomes, demonstrating that WT and A53T neurons exacerbated LD accumulation in glial cells. Moreover, the pesticide maneb triggered ferroptosis associated with aSyn overexpression in neurons with a rise in neutral lipid content (p<0.05). These results suggest that altered lipidostasis could be a hallmark of early aSyn-induced neurodegeneration. Mice exposed to neurotoxicants, as maneb and iron overload, showed aSyn upregulation (p<0.05) in whole brain and midbrain associated with motor impairment. In addition, the loss of tyrosine hydroxylase neurons in midbrain (p<0.001) was related to ferroptosis markers. Midbrain lipid profiles revealed that injured mice presented lipolysis as a consequence of diminished neutral lipid acylation (p<0.01) and lipogenesis, and higher cholesteryl ester deacylation rendering cholesterol accumulation (p<0.05). Neuronal death and movement disorders are linked with active lipolysis in in vivo models. Thus, indicating that marked injury in synucleinopathies is accompanied by impaired LD formation with cholesterol accumulation. Taken together, our results postulate LD as ying/yang markers of different stages of aSyn-induced neurodegeneration
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: 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
Fil: Benzi Juncos, Oriana Nicole. 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: Funk, Melania Iara. 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: Salvador, Gabriela A.. 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
Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Alpha-synuclein (aSyn) pathology is a hallmark in the onset and progression of several synucleinopathies, including Parkinson’s disease. It has been demonstrated that lipid disturbances are associated with aSyn pathology. Our aim was to study neutral lipid metabolism in several in vivo and in vitro models of aSyn accumulation. To this end, different forms of aSyn overexpressed in neurons and toxicant-induced animal models related with synucleinopathies were used. In neuronal cultures, we demonstrated that the overexpression of aSyn (WT and mutant A53T) induced the accumulation of lipid droplets (LD) and free cholesterol (p<0.01). We found that LD biogenesis is a “hormesis mechanism” for preventing neuronal death induced by proteostasis impairment. Neuron-glia crosstalk was evaluated using neuronal secretomes, demonstrating that WT and A53T neurons exacerbated LD accumulation in glial cells. Moreover, the pesticide maneb triggered ferroptosis associated with aSyn overexpression in neurons with a rise in neutral lipid content (p<0.05). These results suggest that altered lipidostasis could be a hallmark of early aSyn-induced neurodegeneration. Mice exposed to neurotoxicants, as maneb and iron overload, showed aSyn upregulation (p<0.05) in whole brain and midbrain associated with motor impairment. In addition, the loss of tyrosine hydroxylase neurons in midbrain (p<0.001) was related to ferroptosis markers. Midbrain lipid profiles revealed that injured mice presented lipolysis as a consequence of diminished neutral lipid acylation (p<0.01) and lipogenesis, and higher cholesteryl ester deacylation rendering cholesterol accumulation (p<0.05). Neuronal death and movement disorders are linked with active lipolysis in in vivo models. Thus, indicating that marked injury in synucleinopathies is accompanied by impaired LD formation with cholesterol accumulation. Taken together, our results postulate LD as ying/yang markers of different stages of aSyn-induced neurodegeneration
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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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/11336/228689
Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies; Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL); Mar del Plata; Argentina; 2023; 70-70
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228689
identifier_str_mv Lipid droplets as Ying-Yang markers of neurodegeneration in models of synucleinopathies; Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL); Mar del Plata; Argentina; 2023; 70-70
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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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