Affiliations: Departamento de Biología Molecular, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain
Correspondence:
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Corresponding author: Javier Díaz-Nido, Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain, Tel.: +34 91 397 8710, Fax: +34 91 397 4799, E-mail: jdnido@cbm.uam.es.
Abstract: 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.
