Phosphorylation of Actin-depolymerizing factor/cofilin by lim-kinase mediates amyloid beta-induced Degeneration: a potential mechanism of neuronal dystrophy in alzheimer's disease

HEREDIA L, HELGUERA P, DE OLMOS S, KEDIKIAN G, SOLÁ VIGO F, LAFERLA F, STAUFENBIEL M, DE OLMOS J, BUSCIGLIO J, CÁCERES A, LORENZO A

SOC NEUROSCIENCE

Lugar: Washington; Año: 2006 vol. 26 p. 6533 - 6533

p>Deposition of fibrillar amyloid beta (fAbeta) plays a critical role in Alzheimer´s disease (AD). We have shown recently that fAbeta-induced dystrophy requires the activation of focal adhesion proteins and the formation of aberrant focal adhesion structures, suggesting the activation of a mechanism of maladaptative plasticity in AD. Focal adhesions are actin-based structures that provide a structural link between the extracellular matrix and the cytoskeleton. To gain additional insight in the molecular mechanism of neuronal degeneration in AD, here we explored the involvement of LIM kinase 1 (LIMK1), actin-depolymerizing factor (ADF), and cofilin in Abeta-induced dystrophy. ADF/cofilin are actin-binding proteins that play a central role in actin filament dynamics, and LIMK1 is the kinase that phosphorylates and thereby inhibits ADF/cofilin. Our data indicate that treatment of hippocampal neurons with fAbeta increases the level of Ser3-phosphorylated ADF/cofilin and Thr508-phosphoryla