Tau Protein as a New Regulator of Cellular Prion Protein Transcription

Cellular prion protein (PrP) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrP. Physiological functions of PrP include protective roles against oxidative stress and excitotoxicity. Relevantly, PrP down...

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Autores: Lidón, Laia, Vergara, Cristina, Ferrer, Isidro, Hernández, Félix, Ávila, Jesús, Río, José Antonio del, Gavín, Rosalina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/254544
Acceso en línea:http://hdl.handle.net/10261/254544
Access Level:acceso abierto
Palabra clave:Cellular prion protein
Tau
Promoters
Alzheimer’s disease
Tauopathies
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spelling Tau Protein as a New Regulator of Cellular Prion Protein TranscriptionLidón, LaiaVergara, CristinaFerrer, IsidroHernández, FélixÁvila, JesúsRío, José Antonio delGavín, RosalinaCellular prion proteinTauPromotersAlzheimer’s diseaseTauopathiesCellular prion protein (PrP) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrP. Physiological functions of PrP include protective roles against oxidative stress and excitotoxicity. Relevantly, PrP downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer’s disease (AD). In addition to the accumulation of misfolded proteins, in the initial stages of AD-affected brains display both increased reactive oxygen species (ROS) markers and levels of PrP. However, the factors responsible for the upregulation of PrP are unknown. Thus, the aim of this study was to uncover the different molecular actors promoting PrP overexpression. In order to mimic early stages of AD, we used β-amyloid-derived diffusible ligands (ADDLs) and tau cellular treatments, as well as ROS generation, to elucidate their particular roles in human PRNP promoter activity. In addition, we used specific chemical inhibitors and site-specific mutations of the PRNP promoter sequence to analyze the contribution of the main transcription factors involved in PRNP transcription under the analyzed conditions. Our results revealed that tau is a new modulator of PrP expression independently of ADDL treatment and ROS levels. Lastly, we discovered that the JNK/c-jun-AP-1 pathway is involved in increased PRNP transcription activity by tau but not in the promoter response to ROS.PRPSEM with reference (RTI2018-099773-B-I00) and PRIONET (AGL2017-90665-REDT), the Generalitat de Catalunya (SGR2017-648), CIBERNED (CNED-2018-2), and CERCA Programme/Generalitat de Catalunya to JADR. The project leading to these results also received funding from “la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR19/52160007 and María de Maeztu Unit of Excellence (Institute of Neurosciences, University of BarcelonaGeneralitat de CatalunyaCentro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)Fundación Caixa GaliciaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/254544reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1007/s12035-020-02025-xSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2545442026-05-22T06:33:51Z
dc.title.none.fl_str_mv Tau Protein as a New Regulator of Cellular Prion Protein Transcription
title Tau Protein as a New Regulator of Cellular Prion Protein Transcription
spellingShingle Tau Protein as a New Regulator of Cellular Prion Protein Transcription
Lidón, Laia
Cellular prion protein
Tau
Promoters
Alzheimer’s disease
Tauopathies
title_short Tau Protein as a New Regulator of Cellular Prion Protein Transcription
title_full Tau Protein as a New Regulator of Cellular Prion Protein Transcription
title_fullStr Tau Protein as a New Regulator of Cellular Prion Protein Transcription
title_full_unstemmed Tau Protein as a New Regulator of Cellular Prion Protein Transcription
title_sort Tau Protein as a New Regulator of Cellular Prion Protein Transcription
dc.creator.none.fl_str_mv Lidón, Laia
Vergara, Cristina
Ferrer, Isidro
Hernández, Félix
Ávila, Jesús
Río, José Antonio del
Gavín, Rosalina
author Lidón, Laia
author_facet Lidón, Laia
Vergara, Cristina
Ferrer, Isidro
Hernández, Félix
Ávila, Jesús
Río, José Antonio del
Gavín, Rosalina
author_role author
author2 Vergara, Cristina
Ferrer, Isidro
Hernández, Félix
Ávila, Jesús
Río, José Antonio del
Gavín, Rosalina
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Generalitat de Catalunya
Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
Fundación Caixa Galicia
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cellular prion protein
Tau
Promoters
Alzheimer’s disease
Tauopathies
topic Cellular prion protein
Tau
Promoters
Alzheimer’s disease
Tauopathies
description Cellular prion protein (PrP) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrP. Physiological functions of PrP include protective roles against oxidative stress and excitotoxicity. Relevantly, PrP downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer’s disease (AD). In addition to the accumulation of misfolded proteins, in the initial stages of AD-affected brains display both increased reactive oxygen species (ROS) markers and levels of PrP. However, the factors responsible for the upregulation of PrP are unknown. Thus, the aim of this study was to uncover the different molecular actors promoting PrP overexpression. In order to mimic early stages of AD, we used β-amyloid-derived diffusible ligands (ADDLs) and tau cellular treatments, as well as ROS generation, to elucidate their particular roles in human PRNP promoter activity. In addition, we used specific chemical inhibitors and site-specific mutations of the PRNP promoter sequence to analyze the contribution of the main transcription factors involved in PRNP transcription under the analyzed conditions. Our results revealed that tau is a new modulator of PrP expression independently of ADDL treatment and ROS levels. Lastly, we discovered that the JNK/c-jun-AP-1 pathway is involved in increased PRNP transcription activity by tau but not in the promoter response to ROS.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/254544
url http://hdl.handle.net/10261/254544
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1007/s12035-020-02025-x
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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