1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death

1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death L Manterola 1,12 , M Hernando-Rodr ı ́ guez 2,12 , A Ruiz 3,4 , A Apraiz 5 , O Arrizabalaga 5 , L Vello ́ n 6 , E Alberdi 3,4 , F Cavaliere 3,4 , HM Lacerda 7 , S Jimenez 8,9 , LA Parada 10 , C Matute 3,4 and JL Zugaza...

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Detalles Bibliográficos
Autores: Manterola, L., Hernando Rodríguez, M., Ruiz, A., Jiménez Muñoz, Sebastián
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/55893
Acceso en línea:http://hdl.handle.net/11441/55893
https://doi.org/10.1038/tp.2012.147
Access Level:acceso abierto
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spelling 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal deathManterola, L.Hernando Rodríguez, M.Ruiz, A.Jiménez Muñoz, Sebastián1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death L Manterola 1,12 , M Hernando-Rodr ı ́ guez 2,12 , A Ruiz 3,4 , A Apraiz 5 , O Arrizabalaga 5 , L Vello ́ n 6 , E Alberdi 3,4 , F Cavaliere 3,4 , HM Lacerda 7 , S Jimenez 8,9 , LA Parada 10 , C Matute 3,4 and JL Zugaza 4,5,11 1–42 b -Amyloid (A b 1–42 ) peptide is a key molecule involved in the development of Alzheimer’s disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of A b 1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, A b 1–42 peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/ phosphoinositol-dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of A b 1–42 peptide in neurons.Nature Publishing GroupBioquímica y Biología Molecular2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/55893https://doi.org/10.1038/tp.2012.147reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésTranslational Psychiatry, 3 (1), 1-12.http://dx.doi.org/10.1038/tp.2012.147info:eu-repo/semantics/openAccessoai:idus.us.es:11441/558932026-06-17T12:51:07Z
dc.title.none.fl_str_mv 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
title 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
spellingShingle 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
Manterola, L.
title_short 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
title_full 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
title_fullStr 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
title_full_unstemmed 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
title_sort 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death
dc.creator.none.fl_str_mv Manterola, L.
Hernando Rodríguez, M.
Ruiz, A.
Jiménez Muñoz, Sebastián
author Manterola, L.
author_facet Manterola, L.
Hernando Rodríguez, M.
Ruiz, A.
Jiménez Muñoz, Sebastián
author_role author
author2 Hernando Rodríguez, M.
Ruiz, A.
Jiménez Muñoz, Sebastián
author2_role author
author
author
dc.contributor.none.fl_str_mv Bioquímica y Biología Molecular
description 1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death L Manterola 1,12 , M Hernando-Rodr ı ́ guez 2,12 , A Ruiz 3,4 , A Apraiz 5 , O Arrizabalaga 5 , L Vello ́ n 6 , E Alberdi 3,4 , F Cavaliere 3,4 , HM Lacerda 7 , S Jimenez 8,9 , LA Parada 10 , C Matute 3,4 and JL Zugaza 4,5,11 1–42 b -Amyloid (A b 1–42 ) peptide is a key molecule involved in the development of Alzheimer’s disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of A b 1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, A b 1–42 peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/ phosphoinositol-dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of A b 1–42 peptide in neurons.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/55893
https://doi.org/10.1038/tp.2012.147
url http://hdl.handle.net/11441/55893
https://doi.org/10.1038/tp.2012.147
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Translational Psychiatry, 3 (1), 1-12.
http://dx.doi.org/10.1038/tp.2012.147
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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