Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo

Autores
da Silva Correia, Angela; Schmitz, Matthias; Fischer, Anna Lisa; da Silva Correia, Susana; Simonetti, Franco Lucio; Saher, Gesine; Goya Maldonado, Roberto; Arora, Amandeep Singh; Fischer, Andre; Outeiro, Tiago F.; Zerr, Inga
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer´s disease (AD), but the precise molecular mechanisms involved in this process are unclear.METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics.RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aβ levels. Light-sheet microscopy showed that PrPC influenced Aβ-plaque burden but not the distribution of those plaques. Interestingly, caveolin-1 (Cav-1) KO neurons significantly reduced intracellular Aβ-oligomer (Aβo) uptake when compared to wild-type neurons.DISCUSSION: The findings shed new light on the relevance of intracellular Aβo, suggesting that PrPC and Cav-1 modulate intracellular Aβ levels and the Aβ-plaque load.
Fil: da Silva Correia, Angela. Universität Göttingen; Alemania
Fil: Schmitz, Matthias. Universität Göttingen; Alemania
Fil: Fischer, Anna Lisa. Universität Göttingen; Alemania
Fil: da Silva Correia, Susana. Universität Göttingen; Alemania
Fil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Saher, Gesine. Max Planck Institute for Multidisciplinary Sciences; Alemania
Fil: Goya Maldonado, Roberto. Universität Göttingen; Alemania
Fil: Arora, Amandeep Singh. University Of Texas Health Science Center At Houston.; Estados Unidos
Fil: Fischer, Andre. Universität Göttingen; Alemania
Fil: Outeiro, Tiago F.. Max Planck Institute For Biophysical Chemistry; Alemania
Fil: Zerr, Inga. Universität Göttingen; Alemania
Materia
Prion
Alzheimer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266335
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266335
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivoda Silva Correia, AngelaSchmitz, MatthiasFischer, Anna Lisada Silva Correia, SusanaSimonetti, Franco LucioSaher, GesineGoya Maldonado, RobertoArora, Amandeep SinghFischer, AndreOuteiro, Tiago F.Zerr, IngaPrionAlzheimerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer´s disease (AD), but the precise molecular mechanisms involved in this process are unclear.METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics.RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aβ levels. Light-sheet microscopy showed that PrPC influenced Aβ-plaque burden but not the distribution of those plaques. Interestingly, caveolin-1 (Cav-1) KO neurons significantly reduced intracellular Aβ-oligomer (Aβo) uptake when compared to wild-type neurons.DISCUSSION: The findings shed new light on the relevance of intracellular Aβo, suggesting that PrPC and Cav-1 modulate intracellular Aβ levels and the Aβ-plaque load.Fil: da Silva Correia, Angela. Universität Göttingen; AlemaniaFil: Schmitz, Matthias. Universität Göttingen; AlemaniaFil: Fischer, Anna Lisa. Universität Göttingen; AlemaniaFil: da Silva Correia, Susana. Universität Göttingen; AlemaniaFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Saher, Gesine. Max Planck Institute for Multidisciplinary Sciences; AlemaniaFil: Goya Maldonado, Roberto. Universität Göttingen; AlemaniaFil: Arora, Amandeep Singh. University Of Texas Health Science Center At Houston.; Estados UnidosFil: Fischer, Andre. Universität Göttingen; AlemaniaFil: Outeiro, Tiago F.. Max Planck Institute For Biophysical Chemistry; AlemaniaFil: Zerr, Inga. Universität Göttingen; AlemaniaWiley2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266335da Silva Correia, Angela; Schmitz, Matthias; Fischer, Anna Lisa; da Silva Correia, Susana; Simonetti, Franco Lucio; et al.; Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo; Wiley; Alzheimers & Dementia; 20; 10; 8-2024; 6776-67921552-5260CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14120info:eu-repo/semantics/altIdentifier/doi/10.1002/alz.14120info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:19Zoai:ri.conicet.gov.ar:11336/266335instacron: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 10:26:19.974CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
title Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
spellingShingle Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
da Silva Correia, Angela
Prion
Alzheimer
title_short Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
title_full Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
title_fullStr Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
title_full_unstemmed Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
title_sort Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo
dc.creator.none.fl_str_mv da Silva Correia, Angela
Schmitz, Matthias
Fischer, Anna Lisa
da Silva Correia, Susana
Simonetti, Franco Lucio
Saher, Gesine
Goya Maldonado, Roberto
Arora, Amandeep Singh
Fischer, Andre
Outeiro, Tiago F.
Zerr, Inga
author da Silva Correia, Angela
author_facet da Silva Correia, Angela
Schmitz, Matthias
Fischer, Anna Lisa
da Silva Correia, Susana
Simonetti, Franco Lucio
Saher, Gesine
Goya Maldonado, Roberto
Arora, Amandeep Singh
Fischer, Andre
Outeiro, Tiago F.
Zerr, Inga
author_role author
author2 Schmitz, Matthias
Fischer, Anna Lisa
da Silva Correia, Susana
Simonetti, Franco Lucio
Saher, Gesine
Goya Maldonado, Roberto
Arora, Amandeep Singh
Fischer, Andre
Outeiro, Tiago F.
Zerr, Inga
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prion
Alzheimer
topic Prion
Alzheimer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer´s disease (AD), but the precise molecular mechanisms involved in this process are unclear.METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics.RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aβ levels. Light-sheet microscopy showed that PrPC influenced Aβ-plaque burden but not the distribution of those plaques. Interestingly, caveolin-1 (Cav-1) KO neurons significantly reduced intracellular Aβ-oligomer (Aβo) uptake when compared to wild-type neurons.DISCUSSION: The findings shed new light on the relevance of intracellular Aβo, suggesting that PrPC and Cav-1 modulate intracellular Aβ levels and the Aβ-plaque load.
Fil: da Silva Correia, Angela. Universität Göttingen; Alemania
Fil: Schmitz, Matthias. Universität Göttingen; Alemania
Fil: Fischer, Anna Lisa. Universität Göttingen; Alemania
Fil: da Silva Correia, Susana. Universität Göttingen; Alemania
Fil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Saher, Gesine. Max Planck Institute for Multidisciplinary Sciences; Alemania
Fil: Goya Maldonado, Roberto. Universität Göttingen; Alemania
Fil: Arora, Amandeep Singh. University Of Texas Health Science Center At Houston.; Estados Unidos
Fil: Fischer, Andre. Universität Göttingen; Alemania
Fil: Outeiro, Tiago F.. Max Planck Institute For Biophysical Chemistry; Alemania
Fil: Zerr, Inga. Universität Göttingen; Alemania
description INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer´s disease (AD), but the precise molecular mechanisms involved in this process are unclear.METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics.RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aβ levels. Light-sheet microscopy showed that PrPC influenced Aβ-plaque burden but not the distribution of those plaques. Interestingly, caveolin-1 (Cav-1) KO neurons significantly reduced intracellular Aβ-oligomer (Aβo) uptake when compared to wild-type neurons.DISCUSSION: The findings shed new light on the relevance of intracellular Aβo, suggesting that PrPC and Cav-1 modulate intracellular Aβ levels and the Aβ-plaque load.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
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/11336/266335
da Silva Correia, Angela; Schmitz, Matthias; Fischer, Anna Lisa; da Silva Correia, Susana; Simonetti, Franco Lucio; et al.; Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo; Wiley; Alzheimers & Dementia; 20; 10; 8-2024; 6776-6792
1552-5260
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266335
identifier_str_mv da Silva Correia, Angela; Schmitz, Matthias; Fischer, Anna Lisa; da Silva Correia, Susana; Simonetti, Franco Lucio; et al.; Cellular prion protein acts as mediator of amyloid beta uptake by caveolin‐1 causing cellular dysfunctions in vitro and in vivo; Wiley; Alzheimers & Dementia; 20; 10; 8-2024; 6776-6792
1552-5260
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://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14120
info:eu-repo/semantics/altIdentifier/doi/10.1002/alz.14120
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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 13.070432

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