Glycogen Synthase Kinase-3 Modulates Neurite Outgrowth in Cultured Neurons: Possible Implications for Neurite Pathology in Alzheimer's Disease.
Glycogen synthase kinase-3 (GSK-3) is thought to play an important role in the hyperphosphorylation of tau, and possibly other proteins, in Alzheimer's disease (AD). However, the effects of GSK-3 on neuronal metabolism are still largely unknown. Here we describe that a low concentration of lithium, which can partially inhibit endogenous GSK-3, favored the extension of neurites from developing neurons, whereas a high concentration of lithium impaired neurite growth. Furthermore, the overexpression of exogenous active GSK-3 in neurons by infection with a defective herpesviral vector blocked neurite growth, which was not affected by either expression of inactive GSK-3 or just the herpesviral vector infection. Neurite extension was restored when neurons overexpressing exogenous active GSK-3 were incubated with lithium. These results are consistent with a role for GSK-3 in the regulation of cytoskeletal dynamics during neurite growth. Accordingly, up-regulation of GSK-3 may contribute to cytoskeletal pathology within neurites in AD.
Muñoz-Montaño
Juan Ramón
JR
Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
Lim
Filip
F
Moreno
Francisco J.
FJ
Avila
Jesús
J
Díaz-Nido
Javier
J