title: 1-42 β-amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death.
abstract: 1-42 β-Amyloid (Aβ(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 Aβ(1-42) peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ(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 Aβ(1-42) peptide in neurons.
authors: Biodonostia Institute, Hospital Donostia, P Doctor Begiristain, Donostia, Spain.
authors: L
authors: L
authors: Manterola
authors: M
authors: M
authors: Hernando-Rodríguez
authors: A
authors: A
authors: Ruiz
authors: A
authors: A
authors: Apraiz
authors: O
authors: O
authors: Arrizabalaga
authors: L
authors: L
authors: Vellón
authors: E
authors: E
authors: Alberdi
authors: F
authors: F
authors: Cavaliere
authors: H M
authors: HM
authors: Lacerda
authors: S
authors: S
authors: Jimenez
authors: L A
authors: LA
authors: Parada
authors: C
authors: C
authors: Matute
authors: J L
authors: JL
authors: Zugaza
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D006801:Humans; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; C578579:Pdpk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein