Resolution components and lipid metabolism as emerging targets in neurodegeneration
- Autores
- Salvador, Gabriela Alejandra
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- Neurodegenerative disorders are characterized by the progressive and selective loss of vulnerable neurons in specific brain areas. Some major harmful challenges associated with neuronal dysfunction and death are proteotoxicity, oxidative stress, and neuroinflammation. By using metabolomics, we detected that phospholipids are selectively hydrolyzed in astrocytes and neurons by several phospholipases A2 in response to toxicity threats. In addition, ferroptosis- associated stimuli produced an imbalance in arachidonic acid (AA) and docosahexaenoic acid (DHA) content. This fatty acid rewiring activated AA- and DHA-dependent resolution pathways to mitigate pro-inflammatory signaling, and lipid droplet accumulation thus promoting cell survival. The inflammation/resolution balance is governed by many specialized pro-resolving lipid mediators acting as ligands of the GPCR receptor FPR2/ALX. In line with this, we also demonstrated that neurons and astrocytes secrete lipid ligands for FPR2/ALX-mediated resolution. Proteotoxic stimulus and oxidative stress also triggered lipid droplet accumulation in neurons and glia. Active lipid droplet hydrolysis and free cholesterol accumulation are associated with gliosis and movement disorders when massive dopaminergic neuronal death occurs in mice midbrain. Thus, depending on the neuronal injury level, lipid droplets can act as protective against damage or as promoters of cellular death. We hypothesize that lipid droplets act as yin/yang effectors of neurodegeneration working as dynamic fatty acid donors or sinks to intervene in resolution or pro-inflammatory signaling. Our results shed light on new targetable metabolic pathways for treating neurodegenerative disorders.
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
LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental
Bahia Blanca
Argentina
Asociación Argentina de Farmacología Experimental - Materia
-
RESOLUTION
NEUROINFLAMMATION
FPR2 - 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:11336/262617
Ver los metadatos del registro completo
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Resolution components and lipid metabolism as emerging targets in neurodegenerationSalvador, Gabriela AlejandraRESOLUTIONNEUROINFLAMMATIONFPR2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Neurodegenerative disorders are characterized by the progressive and selective loss of vulnerable neurons in specific brain areas. Some major harmful challenges associated with neuronal dysfunction and death are proteotoxicity, oxidative stress, and neuroinflammation. By using metabolomics, we detected that phospholipids are selectively hydrolyzed in astrocytes and neurons by several phospholipases A2 in response to toxicity threats. In addition, ferroptosis- associated stimuli produced an imbalance in arachidonic acid (AA) and docosahexaenoic acid (DHA) content. This fatty acid rewiring activated AA- and DHA-dependent resolution pathways to mitigate pro-inflammatory signaling, and lipid droplet accumulation thus promoting cell survival. The inflammation/resolution balance is governed by many specialized pro-resolving lipid mediators acting as ligands of the GPCR receptor FPR2/ALX. In line with this, we also demonstrated that neurons and astrocytes secrete lipid ligands for FPR2/ALX-mediated resolution. Proteotoxic stimulus and oxidative stress also triggered lipid droplet accumulation in neurons and glia. Active lipid droplet hydrolysis and free cholesterol accumulation are associated with gliosis and movement disorders when massive dopaminergic neuronal death occurs in mice midbrain. Thus, depending on the neuronal injury level, lipid droplets can act as protective against damage or as promoters of cellular death. We hypothesize that lipid droplets act as yin/yang effectors of neurodegeneration working as dynamic fatty acid donors or sinks to intervene in resolution or pro-inflammatory signaling. Our results shed light on new targetable metabolic pathways for treating neurodegenerative disorders.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; ArgentinaLVI Reunión Anual de la Asociación Argentina de Farmacología ExperimentalBahia BlancaArgentinaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Farmacología Experimental2024info: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/11336/262617Resolution components and lipid metabolism as emerging targets in neurodegeneration; LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental; Bahia Blanca; Argentina; 2024; 9-9978-631-90806-0-5CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/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 Técnicas2025-09-29T10:37:32Zoai:ri.conicet.gov.ar:11336/262617instacron: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 10:37:32.71CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
title |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
spellingShingle |
Resolution components and lipid metabolism as emerging targets in neurodegeneration Salvador, Gabriela Alejandra RESOLUTION NEUROINFLAMMATION FPR2 |
title_short |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
title_full |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
title_fullStr |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
title_full_unstemmed |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
title_sort |
Resolution components and lipid metabolism as emerging targets in neurodegeneration |
dc.creator.none.fl_str_mv |
Salvador, Gabriela Alejandra |
author |
Salvador, Gabriela Alejandra |
author_facet |
Salvador, Gabriela Alejandra |
author_role |
author |
dc.subject.none.fl_str_mv |
RESOLUTION NEUROINFLAMMATION FPR2 |
topic |
RESOLUTION NEUROINFLAMMATION FPR2 |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Neurodegenerative disorders are characterized by the progressive and selective loss of vulnerable neurons in specific brain areas. Some major harmful challenges associated with neuronal dysfunction and death are proteotoxicity, oxidative stress, and neuroinflammation. By using metabolomics, we detected that phospholipids are selectively hydrolyzed in astrocytes and neurons by several phospholipases A2 in response to toxicity threats. In addition, ferroptosis- associated stimuli produced an imbalance in arachidonic acid (AA) and docosahexaenoic acid (DHA) content. This fatty acid rewiring activated AA- and DHA-dependent resolution pathways to mitigate pro-inflammatory signaling, and lipid droplet accumulation thus promoting cell survival. The inflammation/resolution balance is governed by many specialized pro-resolving lipid mediators acting as ligands of the GPCR receptor FPR2/ALX. In line with this, we also demonstrated that neurons and astrocytes secrete lipid ligands for FPR2/ALX-mediated resolution. Proteotoxic stimulus and oxidative stress also triggered lipid droplet accumulation in neurons and glia. Active lipid droplet hydrolysis and free cholesterol accumulation are associated with gliosis and movement disorders when massive dopaminergic neuronal death occurs in mice midbrain. Thus, depending on the neuronal injury level, lipid droplets can act as protective against damage or as promoters of cellular death. We hypothesize that lipid droplets act as yin/yang effectors of neurodegeneration working as dynamic fatty acid donors or sinks to intervene in resolution or pro-inflammatory signaling. Our results shed light on new targetable metabolic pathways for treating neurodegenerative disorders. 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 LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental Bahia Blanca Argentina Asociación Argentina de Farmacología Experimental |
description |
Neurodegenerative disorders are characterized by the progressive and selective loss of vulnerable neurons in specific brain areas. Some major harmful challenges associated with neuronal dysfunction and death are proteotoxicity, oxidative stress, and neuroinflammation. By using metabolomics, we detected that phospholipids are selectively hydrolyzed in astrocytes and neurons by several phospholipases A2 in response to toxicity threats. In addition, ferroptosis- associated stimuli produced an imbalance in arachidonic acid (AA) and docosahexaenoic acid (DHA) content. This fatty acid rewiring activated AA- and DHA-dependent resolution pathways to mitigate pro-inflammatory signaling, and lipid droplet accumulation thus promoting cell survival. The inflammation/resolution balance is governed by many specialized pro-resolving lipid mediators acting as ligands of the GPCR receptor FPR2/ALX. In line with this, we also demonstrated that neurons and astrocytes secrete lipid ligands for FPR2/ALX-mediated resolution. Proteotoxic stimulus and oxidative stress also triggered lipid droplet accumulation in neurons and glia. Active lipid droplet hydrolysis and free cholesterol accumulation are associated with gliosis and movement disorders when massive dopaminergic neuronal death occurs in mice midbrain. Thus, depending on the neuronal injury level, lipid droplets can act as protective against damage or as promoters of cellular death. We hypothesize that lipid droplets act as yin/yang effectors of neurodegeneration working as dynamic fatty acid donors or sinks to intervene in resolution or pro-inflammatory signaling. Our results shed light on new targetable metabolic pathways for treating neurodegenerative disorders. |
publishDate |
2024 |
dc.date.none.fl_str_mv |
2024 |
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/11336/262617 Resolution components and lipid metabolism as emerging targets in neurodegeneration; LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental; Bahia Blanca; Argentina; 2024; 9-9 978-631-90806-0-5 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/262617 |
identifier_str_mv |
Resolution components and lipid metabolism as emerging targets in neurodegeneration; LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental; Bahia Blanca; Argentina; 2024; 9-9 978-631-90806-0-5 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://aafeargentina.org/congresos-aafe/ |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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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 |
Asociación Argentina de Farmacología Experimental |
publisher.none.fl_str_mv |
Asociación Argentina de Farmacología Experimental |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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