Effect of glycogen synthase kinase-3 overactivation on neurofilament phosphorylation

Objective: To investigate the effect of glycogen synthase kinase-3 (GSK-3) overactivation on neurofilament phosphorylation in cultured cells. Methods: After N2a cells were treated with wortmannin or with wortmannin and LiCl, the GSK-3 activity and neurofilament phosphorylation were detected by GSK-3 activity assay, Western blots and immunofluoresence. Results: It was found that overactivation of GSK-3 induced hyperphosphorylation of neurofilament. Overactivation of GSK-3 led to a reduced staining with antibody SMI32 and an enhanced staining with antibody SMI31. Conclusion: These results indicate that in vitro over activation of GSK-3 may lead to neurofilament hyperphosphorylation and this may be the underlying mechanism of Alzheimer's disease.