Your browser doesn't support javascript.
loading
Fibrillar amyloid-ß1-42 modifies actin organization affecting the cofilin phosphorylation state: a role for Rac1/cdc42 effector proteins and the slingshot phosphatase.
Mendoza-Naranjo, Ariadna; Contreras-Vallejos, Erick; Henriquez, Daniel R; Otth, Carola; Bamburg, James R; Maccioni, Ricardo B; Gonzalez-Billault, Christian.
Afiliação
  • Mendoza-Naranjo A; Laboratory of Cellular and Molecular Neurosciences, University of Chile and International Center for Biomedicine (ICC), Santiago, Chile.
J Alzheimers Dis ; 29(1): 63-77, 2012.
Article em En | MEDLINE | ID: mdl-22204905
The neuronal cytoskeleton regulates numerous processes that occur in normal homeostasis. Under pathological conditions such as those of Alzheimer's disease (AD), major alterations in cytoskeleton organization have been observed and changes in both microtubules and actin filaments have been reported. Many neurodegenerative consequences of AD are linked to the production and accumulation of amyloid peptides (Aß) and their oligomers, produced from the internal cleavage of the amyloid-ß protein precursor. We previously reported that fibrillar Aß1-42 (fAß) treatment of hippocampal neurons induced an increase in Rac1 and Cdc42 activities linking fAß effects with changes in actin dynamics. Here we show fAß-induces increased activity of PAK1 and cyclin-dependent kinase 5, and that p21-activated kinase (PAK1) activation targets the LIMK1-cofilin signaling pathway. Increased cofilin dephosphorylation under conditions of enhanced LIM-Kinase 1 (LIMK1) activity suggests that fAß co-stimulates bifurcating pathways impacting cofilin phosphorylation. Overexpression of slingshot (SSH) prevents the augment of F-actin induced by fAß after 24 h, suggesting that fAß-induced changes in actin assembly involve both LIMK1 and SSH. These results suggest that fAb may alter the PAK1/LIMK1/cofilin axis and therefore actin organization in AD.
Assuntos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Neuropeptídeos / Peptídeos beta-Amiloides / Actinas / Fosfoproteínas Fosfatases / Proteína cdc42 de Ligação ao GTP / Proteínas rac de Ligação ao GTP / Fatores de Despolimerização de Actina / Amiloide Limite: Animals Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Neuropeptídeos / Peptídeos beta-Amiloides / Actinas / Fosfoproteínas Fosfatases / Proteína cdc42 de Ligação ao GTP / Proteínas rac de Ligação ao GTP / Fatores de Despolimerização de Actina / Amiloide Limite: Animals Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda