GSK3 and tau: Two convergence points in Alzheimer's disease

Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed serine/threonine kinase that plays a key role in the pathogenesis of Alzheimer's disease (AD). GSK3 phosphorylates tau in most serine and threonine residues hyperphosphorylated in paired helical filaments, and GSK3 activity contribut...

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Detalhes bibliográficos
Autores: Hernández Pérez, Félix, Lucas, José Javier, Ávila, Jesús
Formato: artículo
Fecha de publicación:2012
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/115958
Acesso em linha:http://hdl.handle.net/10261/115958
Access Level:acceso abierto
Palavra-chave:GSK3
Tau
Alzheimer’s disease
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spelling GSK3 and tau: Two convergence points in Alzheimer's diseaseHernández Pérez, FélixLucas, José JavierÁvila, JesúsGSK3TauAlzheimer’s diseaseGlycogen synthase kinase 3 (GSK3) is a ubiquitously expressed serine/threonine kinase that plays a key role in the pathogenesis of Alzheimer's disease (AD). GSK3 phosphorylates tau in most serine and threonine residues hyperphosphorylated in paired helical filaments, and GSK3 activity contributes both to amyloid-β production and amyloid-β-mediated neuronal death. Thus, mice generated in our laboratory with conditional overexpression of GSK3 in forebrain neurons (Tet/GSK3β mice) recapitulate aspects of AD neuropathology such as tau hyperphosphorylation, apoptotic neuronal death, and reactive astrocytosis, as well as spatial learning deficit. In this review, we describe recent contributions of our group showing that transgene shutdown in that animal model leads to normal GSK3 activity, normal phospho-tau levels, diminished neuronal death, and suppression of the cognitive deficit, thus further supporting the potential of GSK3 inhibitors for AD therapeutics. In addition, we have combined transgenic mice overexpressing the enzyme GSK3β with transgenic mice expressing tau with a triple FTDP-17 mutation that develop prefibrillar tau-aggregates. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Further, it is possible to partially reverse tau pathology in advanced stages of the disease, although the presence of already assembled neurofibrillary tangle-like structures cannot be reversed. © 2013 The authors and IOS Press. All rights reserved.Peer Reviewed2015201520122015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/115958reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1159582026-05-22T06:33:51Z
dc.title.none.fl_str_mv GSK3 and tau: Two convergence points in Alzheimer's disease
title GSK3 and tau: Two convergence points in Alzheimer's disease
spellingShingle GSK3 and tau: Two convergence points in Alzheimer's disease
Hernández Pérez, Félix
GSK3
Tau
Alzheimer’s disease
title_short GSK3 and tau: Two convergence points in Alzheimer's disease
title_full GSK3 and tau: Two convergence points in Alzheimer's disease
title_fullStr GSK3 and tau: Two convergence points in Alzheimer's disease
title_full_unstemmed GSK3 and tau: Two convergence points in Alzheimer's disease
title_sort GSK3 and tau: Two convergence points in Alzheimer's disease
dc.creator.none.fl_str_mv Hernández Pérez, Félix
Lucas, José Javier
Ávila, Jesús
author Hernández Pérez, Félix
author_facet Hernández Pérez, Félix
Lucas, José Javier
Ávila, Jesús
author_role author
author2 Lucas, José Javier
Ávila, Jesús
author2_role author
author
dc.subject.none.fl_str_mv GSK3
Tau
Alzheimer’s disease
topic GSK3
Tau
Alzheimer’s disease
description Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed serine/threonine kinase that plays a key role in the pathogenesis of Alzheimer's disease (AD). GSK3 phosphorylates tau in most serine and threonine residues hyperphosphorylated in paired helical filaments, and GSK3 activity contributes both to amyloid-β production and amyloid-β-mediated neuronal death. Thus, mice generated in our laboratory with conditional overexpression of GSK3 in forebrain neurons (Tet/GSK3β mice) recapitulate aspects of AD neuropathology such as tau hyperphosphorylation, apoptotic neuronal death, and reactive astrocytosis, as well as spatial learning deficit. In this review, we describe recent contributions of our group showing that transgene shutdown in that animal model leads to normal GSK3 activity, normal phospho-tau levels, diminished neuronal death, and suppression of the cognitive deficit, thus further supporting the potential of GSK3 inhibitors for AD therapeutics. In addition, we have combined transgenic mice overexpressing the enzyme GSK3β with transgenic mice expressing tau with a triple FTDP-17 mutation that develop prefibrillar tau-aggregates. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Further, it is possible to partially reverse tau pathology in advanced stages of the disease, although the presence of already assembled neurofibrillary tangle-like structures cannot be reversed. © 2013 The authors and IOS Press. All rights reserved.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/115958
url http://hdl.handle.net/10261/115958
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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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