Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup

Autores
Guix, Francesc X.; Marrero Capitán, Ana; Casadomé Perales, Álvaro; Palomares Pérez, Irene; Lopez del Castillo, Irene; Miguel, Verónica; Goedeke, Leigh; Martín, Mauricio Gerardo; Lamas, Santiago; Peinado, Héctor; Fernández Hernando, Carlos; Dotti, Carlos
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
As neurons age, they show a decrease in their ability to degrade proteins and membranes. Because undegraded material is a source of toxic products, defects in degradation are associated with reduced cell function and survival. However, there are very few dead neurons in the aging brain, suggesting the action of compensatory mechanisms. We show in this work that ageing neurons in culture show large multivesicular bodies (MVBs) filled with intralumenal vesicles (ILVs) and secrete more small extracellular vesicles than younger neurons. We also show that the high number of ILVs is the consequence of the accumulation of cholesterol in MVBs, which in turn is due to decreased levels of the cholesterol extruding protein NPC1. NPC1 down-regulation is the consequence of a combination of upregulation of the NPC1 repressor microRNA 33, and increased degradation, due to AktmTOR targeting of NPC1 to the phagosome. Although releasing more exosomes can be beneficial to old neurons, other cells, neighbouring and distant, can be negatively affected by the waste material they contain.
Fil: Guix, Francesc X.. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Marrero Capitán, Ana. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Casadomé Perales, Álvaro. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Palomares Pérez, Irene. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Lopez del Castillo, Irene. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Miguel, Verónica. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Goedeke, Leigh. University of Yale; Estados Unidos
Fil: Martín, Mauricio Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Lamas, Santiago. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Peinado, Héctor. Centro Nacional de Investigaciones Oncológicas; España
Fil: Fernández Hernando, Carlos. University of Yale; Estados Unidos
Fil: Dotti, Carlos. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; España
Materia
EXOSOMES
CHOLESTEROL
NEURONAL
AGING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/167285
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/167285
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildupGuix, Francesc X.Marrero Capitán, AnaCasadomé Perales, ÁlvaroPalomares Pérez, IreneLopez del Castillo, IreneMiguel, VerónicaGoedeke, LeighMartín, Mauricio GerardoLamas, SantiagoPeinado, HéctorFernández Hernando, CarlosDotti, CarlosEXOSOMESCHOLESTEROLNEURONALAGINGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1As neurons age, they show a decrease in their ability to degrade proteins and membranes. Because undegraded material is a source of toxic products, defects in degradation are associated with reduced cell function and survival. However, there are very few dead neurons in the aging brain, suggesting the action of compensatory mechanisms. We show in this work that ageing neurons in culture show large multivesicular bodies (MVBs) filled with intralumenal vesicles (ILVs) and secrete more small extracellular vesicles than younger neurons. We also show that the high number of ILVs is the consequence of the accumulation of cholesterol in MVBs, which in turn is due to decreased levels of the cholesterol extruding protein NPC1. NPC1 down-regulation is the consequence of a combination of upregulation of the NPC1 repressor microRNA 33, and increased degradation, due to AktmTOR targeting of NPC1 to the phagosome. Although releasing more exosomes can be beneficial to old neurons, other cells, neighbouring and distant, can be negatively affected by the waste material they contain.Fil: Guix, Francesc X.. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Marrero Capitán, Ana. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Casadomé Perales, Álvaro. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Palomares Pérez, Irene. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Lopez del Castillo, Irene. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Miguel, Verónica. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Goedeke, Leigh. University of Yale; Estados UnidosFil: Martín, Mauricio Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Lamas, Santiago. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Peinado, Héctor. Centro Nacional de Investigaciones Oncológicas; EspañaFil: Fernández Hernando, Carlos. University of Yale; Estados UnidosFil: Dotti, Carlos. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; EspañaRockefeller University Press2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/167285Guix, Francesc X.; Marrero Capitán, Ana; Casadomé Perales, Álvaro; Palomares Pérez, Irene; Lopez del Castillo, Irene; et al.; Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup; Rockefeller University Press; Life Science Alliance; 4; 8; 6-2021; 1-182575-1077CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.26508/LSA.202101055info:eu-repo/semantics/altIdentifier/url/https://www.life-science-alliance.org/lookup/doi/10.26508/lsa.202101055info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:31Zoai:ri.conicet.gov.ar:11336/167285instacron: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 09:53:31.775CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
title Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
spellingShingle Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
Guix, Francesc X.
EXOSOMES
CHOLESTEROL
NEURONAL
AGING
title_short Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
title_full Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
title_fullStr Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
title_full_unstemmed Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
title_sort Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup
dc.creator.none.fl_str_mv Guix, Francesc X.
Marrero Capitán, Ana
Casadomé Perales, Álvaro
Palomares Pérez, Irene
Lopez del Castillo, Irene
Miguel, Verónica
Goedeke, Leigh
Martín, Mauricio Gerardo
Lamas, Santiago
Peinado, Héctor
Fernández Hernando, Carlos
Dotti, Carlos
author Guix, Francesc X.
author_facet Guix, Francesc X.
Marrero Capitán, Ana
Casadomé Perales, Álvaro
Palomares Pérez, Irene
Lopez del Castillo, Irene
Miguel, Verónica
Goedeke, Leigh
Martín, Mauricio Gerardo
Lamas, Santiago
Peinado, Héctor
Fernández Hernando, Carlos
Dotti, Carlos
author_role author
author2 Marrero Capitán, Ana
Casadomé Perales, Álvaro
Palomares Pérez, Irene
Lopez del Castillo, Irene
Miguel, Verónica
Goedeke, Leigh
Martín, Mauricio Gerardo
Lamas, Santiago
Peinado, Héctor
Fernández Hernando, Carlos
Dotti, Carlos
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EXOSOMES
CHOLESTEROL
NEURONAL
AGING
topic EXOSOMES
CHOLESTEROL
NEURONAL
AGING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv As neurons age, they show a decrease in their ability to degrade proteins and membranes. Because undegraded material is a source of toxic products, defects in degradation are associated with reduced cell function and survival. However, there are very few dead neurons in the aging brain, suggesting the action of compensatory mechanisms. We show in this work that ageing neurons in culture show large multivesicular bodies (MVBs) filled with intralumenal vesicles (ILVs) and secrete more small extracellular vesicles than younger neurons. We also show that the high number of ILVs is the consequence of the accumulation of cholesterol in MVBs, which in turn is due to decreased levels of the cholesterol extruding protein NPC1. NPC1 down-regulation is the consequence of a combination of upregulation of the NPC1 repressor microRNA 33, and increased degradation, due to AktmTOR targeting of NPC1 to the phagosome. Although releasing more exosomes can be beneficial to old neurons, other cells, neighbouring and distant, can be negatively affected by the waste material they contain.
Fil: Guix, Francesc X.. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Marrero Capitán, Ana. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Casadomé Perales, Álvaro. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Palomares Pérez, Irene. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Lopez del Castillo, Irene. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Miguel, Verónica. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Goedeke, Leigh. University of Yale; Estados Unidos
Fil: Martín, Mauricio Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Lamas, Santiago. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; España
Fil: Peinado, Héctor. Centro Nacional de Investigaciones Oncológicas; España
Fil: Fernández Hernando, Carlos. University of Yale; Estados Unidos
Fil: Dotti, Carlos. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; España
description As neurons age, they show a decrease in their ability to degrade proteins and membranes. Because undegraded material is a source of toxic products, defects in degradation are associated with reduced cell function and survival. However, there are very few dead neurons in the aging brain, suggesting the action of compensatory mechanisms. We show in this work that ageing neurons in culture show large multivesicular bodies (MVBs) filled with intralumenal vesicles (ILVs) and secrete more small extracellular vesicles than younger neurons. We also show that the high number of ILVs is the consequence of the accumulation of cholesterol in MVBs, which in turn is due to decreased levels of the cholesterol extruding protein NPC1. NPC1 down-regulation is the consequence of a combination of upregulation of the NPC1 repressor microRNA 33, and increased degradation, due to AktmTOR targeting of NPC1 to the phagosome. Although releasing more exosomes can be beneficial to old neurons, other cells, neighbouring and distant, can be negatively affected by the waste material they contain.
publishDate 2021
dc.date.none.fl_str_mv 2021-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/167285
Guix, Francesc X.; Marrero Capitán, Ana; Casadomé Perales, Álvaro; Palomares Pérez, Irene; Lopez del Castillo, Irene; et al.; Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup; Rockefeller University Press; Life Science Alliance; 4; 8; 6-2021; 1-18
2575-1077
CONICET Digital
CONICET
url http://hdl.handle.net/11336/167285
identifier_str_mv Guix, Francesc X.; Marrero Capitán, Ana; Casadomé Perales, Álvaro; Palomares Pérez, Irene; Lopez del Castillo, Irene; et al.; Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup; Rockefeller University Press; Life Science Alliance; 4; 8; 6-2021; 1-18
2575-1077
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.26508/LSA.202101055
info:eu-repo/semantics/altIdentifier/url/https://www.life-science-alliance.org/lookup/doi/10.26508/lsa.202101055
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
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 12.885934

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