| Glycogen synthase kinase-3 (GSK-3) is a serine/threonine, proline directed kinase involved in a diverse array of signaling pathways, including glycogen synthesis and cellular adhesion and is implicated in Alzheimers disease. Two forms of GSK-3, designated GSK-3(alpha) and GSK-3(beta), are related yet they differ in their subcellular localization. The microtubule binding protein, Tau, serves to stabilize microtubules in growing axons. Tau is found to be hyperphosphorylated in paired helical filaments (PHF), the major fibrous component of neurofibrillary lesions associated with Alzheimers disease. Hyperphosphorylation of Tau is thought to be the critical event leading to the assembly of PHF. Six Tau protein isoforms have been identified, all of which are phosphorylated by GSK-3, presenting the possibility that miscues in GSK-3 signaling contribute to the onset of Alzheimers disease. |
