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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/262617
Acceder
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network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-15T15:34:53Zoai: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:34982025-10-15 15:34:54.118CONICET 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/
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 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
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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score 13.22299

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