Fibrillar amyloid-ß1-42 modifies actin organization affecting the cofilin phosphorylation state: a role for Rac1/cdc42 effector proteins and the slingshot phosphatase.
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.
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