Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients

31 p.-5 fig.-1 tab.

Detalles Bibliográficos
Autores: Posa, Diana, Martínez-González, Loreto, Bartolomé Robledo, Fernando, Siranjeevi, Nagaraj, Porras, Gracia, Martínez Gil, Ana, Martín-Requero, Ángeles
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/167877
Acceso en línea:http://hdl.handle.net/10261/167877
Access Level:acceso abierto
Palabra clave:ALS
Lymphoblasts
TDP-43
CK-1δ
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spelling Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patientsPosa, DianaMartínez-González, LoretoBartolomé Robledo, FernandoSiranjeevi, NagarajPorras, GraciaMartínez Gil, AnaMartín-Requero, ÁngelesALSLymphoblastsTDP-43CK-1δ31 p.-5 fig.-1 tab.Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder of still unknown etiology that results in loss of motoneurons, paralysis, and death, usually between 2 and 4 years from onset. There are no currently available ALS biomarkers to support early diagnosis and to facilitate the assessment of the efficacy of new treatments. Since ALS is considered a multisystemic disease, here we have investigated the usefulness of immortalized lymphocytes from sporadic ALS patients to study TDP-43 homeostasis as well as to provide a convenient platform to evaluate TDP-43 phosphorylation as a novel therapeutic approach for ALS. We report here that lymphoblasts from ALS patients recapitulate the hallmarks of TDP-43 processing in affected motoneurons, such as increased phosphorylation, truncation, and mislocalization of TDP-43. Moreover, modulation of TDP-43 by an in-house designed protein casein kinase-1δ (CK-1δ) inhibitor, IGS3.27, reduced phosphorylation of TDP-43, and normalized the nucleo-cytosol translocation of TDP-43 in ALS lymphoblasts. Therefore, we conclude that lymphoblasts, easily accessible cells, from ALS patients could be a useful model to study pathological features of ALS disease and a suitable platform to test the effects of potential disease-modifying drugs even in a personalized manner.This work has been supported by grants from MINECO (CTQ2015-66313-R to A.M.-R. and SAF2016-76693-R to A.M.) and Madrid Community (B2017/BMD3813 ELA-Madrid).Peer reviewedHumana PressMinisterio de Economía y Competitividad (España)Comunidad de MadridBartolomé Robledo, Fernando [0000-0001-9322-8933]Martín-Requero, Ángeles [0000-0002-3416-9440]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201820182018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/167877reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-66313-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76693-Rhttps://doi.org/10.1007/s12035-018-1249-8Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1678772026-05-22T06:33:51Z
dc.title.none.fl_str_mv Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
title Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
spellingShingle Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
Posa, Diana
ALS
Lymphoblasts
TDP-43
CK-1δ
title_short Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
title_full Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
title_fullStr Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
title_full_unstemmed Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
title_sort Recapitulation of pathological TDP-43 features in immortalized lymphocytes from sporadic ALS patients
dc.creator.none.fl_str_mv Posa, Diana
Martínez-González, Loreto
Bartolomé Robledo, Fernando
Siranjeevi, Nagaraj
Porras, Gracia
Martínez Gil, Ana
Martín-Requero, Ángeles
author Posa, Diana
author_facet Posa, Diana
Martínez-González, Loreto
Bartolomé Robledo, Fernando
Siranjeevi, Nagaraj
Porras, Gracia
Martínez Gil, Ana
Martín-Requero, Ángeles
author_role author
author2 Martínez-González, Loreto
Bartolomé Robledo, Fernando
Siranjeevi, Nagaraj
Porras, Gracia
Martínez Gil, Ana
Martín-Requero, Ángeles
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
Bartolomé Robledo, Fernando [0000-0001-9322-8933]
Martín-Requero, Ángeles [0000-0002-3416-9440]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv ALS
Lymphoblasts
TDP-43
CK-1δ
topic ALS
Lymphoblasts
TDP-43
CK-1δ
description 31 p.-5 fig.-1 tab.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/167877
url http://hdl.handle.net/10261/167877
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-66313-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76693-R
https://doi.org/10.1007/s12035-018-1249-8
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Humana Press
publisher.none.fl_str_mv Humana Press
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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score 15,81155

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