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


Autoria(s): Manterola, L.; Hernando Rodríguez, M.; Ruiz Núñez, Asier; Apraiz, A.; Arrizabalaga, O.; Vellon, L.; Alberdi Alfonso, Elena María; Cavaliere, Fabio; Lacerda, H. M.; Jimenez, S.; Parada, L. A.; Matute Almau, Carlos José; Zugaza Gurruchaga, José Luis
Data(s)

04/02/2014

04/02/2014

01/01/2013

Resumo

1-42 beta-Amyloid (A beta(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 beta(1-42) peptide activation of the neurodegenerative program is still poorly understood. Here, A beta(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 beta(1-42) peptide in neurons.

Identificador

Translational Psychiatry 3 : (2013) // e219

2158-3188

http://hdl.handle.net/10810/11340

Idioma(s)

eng

Publicador

Nature Publishing Group

Relação

http://www.nature.com/tp/journal/v3/n1/full/tp2012147a.html

Direitos

(c)2013 Manterola et al., licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

info:eu-repo/semantics/openAccess

Palavras-Chave #A beta(1-42) #neuronal death program #Rac 1 GTPase
Tipo

info:eu-repo/semantics/article