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; SOLA VIGO F; LAFERLA F; STAUFENBIEL M; DE OLMOS J; BUSCIGLIO J; CACERES A; LORENZO A

JOURNAL OF NEUROSCIENCE

Society for Neuroscience

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

0270-6474

p class="abstract">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 T