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

Authors
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
Publication Year
2013
Language
English
Format
article
Status
Published version
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.
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
Subject
RAC 1 GTPASE
NEURONAL DEATH PROGRAM
AB1–42
Neurociencias
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/7618