1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death

Autores
Manterola, L.; Hernando Rodriguez, M.; Ruiz, A.; Apraiz, A.; Arrizabalaga, O.; Vellon, L.; Alberdi, E.; Cavaliere, F.; Lacerda, H.M.; Jimenez, S.; Parada, Luis Antonio; Matute, C.; Zugaza, Jose Luis
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
1–42 β-Amyloid (Aβ1–42) 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 Aβ1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ1–42 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 Aβ1–42 peptide in neurons.
Fil: Manterola, L.. Biodonostia Institute, Hospital Donostia; España
Fil: Hernando Rodriguez, M.. National Cancer Research Center; España
Fil: Ruiz, A.. Universidad del Pais Vasco; España. Achucarro Basque Center for Neuroscience; España
Fil: Apraiz, A.. Universidad del Pais Vasco; España
Fil: Arrizabalaga, O.. Universidad del Pais Vasco; España
Fil: Vellon, L.. Fundación Instituto de Investigación Biomédica y Desarrollo Tecnológico (INBIOMED); España
Fil: Alberdi, E.. Universidad del Pais Vasco; España
Fil: Cavaliere, F.. Universidad del Pais Vasco; España
Fil: Lacerda, H.M.. Università degli Studi di Torino; Italia
Fil: Jimenez, S.. Universidad de Sevilla; España. Consejo Superior de Investigaciones Cientificas; España
Fil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Fil: Matute, C.. Universidad del Pais Vasco; España
Fil: Zugaza, Jose Luis. Universidad del Pais Vasco; España. Bizkaia Science and Technology Park; España
Materia
RAC 1 GTPASE
NEURONAL DEATH PROGRAM
AB1–42
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7618
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/7618
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal deathManterola, L.Hernando Rodriguez, M.Ruiz, A.Apraiz, A.Arrizabalaga, O.Vellon, L.Alberdi, E.Cavaliere, F.Lacerda, H.M.Jimenez, S.Parada, Luis AntonioMatute, C.Zugaza, Jose LuisRAC 1 GTPASENEURONAL DEATH PROGRAMAB1–42https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/31–42 β-Amyloid (Aβ1–42) 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 Aβ1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ1–42 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 Aβ1–42 peptide in neurons.Fil: Manterola, L.. Biodonostia Institute, Hospital Donostia; EspañaFil: Hernando Rodriguez, M.. National Cancer Research Center; EspañaFil: Ruiz, A.. Universidad del Pais Vasco; España. Achucarro Basque Center for Neuroscience; EspañaFil: Apraiz, A.. Universidad del Pais Vasco; EspañaFil: Arrizabalaga, O.. Universidad del Pais Vasco; EspañaFil: Vellon, L.. Fundación Instituto de Investigación Biomédica y Desarrollo Tecnológico (INBIOMED); EspañaFil: Alberdi, E.. Universidad del Pais Vasco; EspañaFil: Cavaliere, F.. Universidad del Pais Vasco; EspañaFil: Lacerda, H.M.. Università degli Studi di Torino; ItaliaFil: Jimenez, S.. Universidad de Sevilla; España. Consejo Superior de Investigaciones Cientificas; EspañaFil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; ArgentinaFil: Matute, C.. Universidad del Pais Vasco; EspañaFil: Zugaza, Jose Luis. Universidad del Pais Vasco; España. Bizkaia Science and Technology Park; EspañaNature Publishing Group2013-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7618Manterola, L.; Hernando Rodriguez, M.; Ruiz, A.; Apraiz, A.; Arrizabalaga, O.; et al.; 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death; Nature Publishing Group; Translational Psychiatry; 3; 1; 1-2013; 219-2192158-3188enginfo:eu-repo/semantics/altIdentifier/doi/10.1038/tp.2012.147info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566727/info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/tp/journal/v3/n1/full/tp2012147a.htmlinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:40Zoai:ri.conicet.gov.ar:11336/7618instacron: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:34982025-09-03 09:55:40.636CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
title 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
spellingShingle 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
Manterola, L.
RAC 1 GTPASE
NEURONAL DEATH PROGRAM
AB1–42
title_short 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
title_full 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
title_fullStr 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
title_full_unstemmed 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
title_sort 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death
dc.creator.none.fl_str_mv Manterola, L.
Hernando Rodriguez, M.
Ruiz, A.
Apraiz, A.
Arrizabalaga, O.
Vellon, L.
Alberdi, E.
Cavaliere, F.
Lacerda, H.M.
Jimenez, S.
Parada, Luis Antonio
Matute, C.
Zugaza, Jose Luis
author Manterola, L.
author_facet Manterola, L.
Hernando Rodriguez, M.
Ruiz, A.
Apraiz, A.
Arrizabalaga, O.
Vellon, L.
Alberdi, E.
Cavaliere, F.
Lacerda, H.M.
Jimenez, S.
Parada, Luis Antonio
Matute, C.
Zugaza, Jose Luis
author_role author
author2 Hernando Rodriguez, M.
Ruiz, A.
Apraiz, A.
Arrizabalaga, O.
Vellon, L.
Alberdi, E.
Cavaliere, F.
Lacerda, H.M.
Jimenez, S.
Parada, Luis Antonio
Matute, C.
Zugaza, Jose Luis
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RAC 1 GTPASE
NEURONAL DEATH PROGRAM
AB1–42
topic RAC 1 GTPASE
NEURONAL DEATH PROGRAM
AB1–42
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 1–42 β-Amyloid (Aβ1–42) 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 Aβ1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ1–42 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 Aβ1–42 peptide in neurons.
Fil: Manterola, L.. Biodonostia Institute, Hospital Donostia; España
Fil: Hernando Rodriguez, M.. National Cancer Research Center; España
Fil: Ruiz, A.. Universidad del Pais Vasco; España. Achucarro Basque Center for Neuroscience; España
Fil: Apraiz, A.. Universidad del Pais Vasco; España
Fil: Arrizabalaga, O.. Universidad del Pais Vasco; España
Fil: Vellon, L.. Fundación Instituto de Investigación Biomédica y Desarrollo Tecnológico (INBIOMED); España
Fil: Alberdi, E.. Universidad del Pais Vasco; España
Fil: Cavaliere, F.. Universidad del Pais Vasco; España
Fil: Lacerda, H.M.. Università degli Studi di Torino; Italia
Fil: Jimenez, S.. Universidad de Sevilla; España. Consejo Superior de Investigaciones Cientificas; España
Fil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Fil: Matute, C.. Universidad del Pais Vasco; España
Fil: Zugaza, Jose Luis. Universidad del Pais Vasco; España. Bizkaia Science and Technology Park; España
description 1–42 β-Amyloid (Aβ1–42) 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 Aβ1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ1–42 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 Aβ1–42 peptide in neurons.
publishDate 2013
dc.date.none.fl_str_mv 2013-01
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/11336/7618
Manterola, L.; Hernando Rodriguez, M.; Ruiz, A.; Apraiz, A.; Arrizabalaga, O.; et al.; 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death; Nature Publishing Group; Translational Psychiatry; 3; 1; 1-2013; 219-219
2158-3188
url http://hdl.handle.net/11336/7618
identifier_str_mv Manterola, L.; Hernando Rodriguez, M.; Ruiz, A.; Apraiz, A.; Arrizabalaga, O.; et al.; 1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death; Nature Publishing Group; Translational Psychiatry; 3; 1; 1-2013; 219-219
2158-3188
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/tp.2012.147
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566727/
info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/tp/journal/v3/n1/full/tp2012147a.html
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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: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 13.13397

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