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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 352805, 11 pages
Review Article

Functional Implications of Glycogen Synthase Kinase-3-Mediated Tau Phosphorylation

Department of Neuroscience (P037), MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

Received 15 April 2011; Accepted 6 May 2011

Academic Editor: Adam Cole

Copyright © 2011 Diane P. Hanger and Wendy Noble. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Tau is primarily a neuronal microtubule-associated protein that has functions related to the stabilisation of microtubules. Phosphorylation of tau is an important dynamic and regulatory element involved in the binding of tau to tubulin. Thus, highly phosphorylated tau is more likely to be present in the cytosolic compartment of neurons, whereas reduced phosphate burden allows tau to bind to and stabilise the microtubule cytoskeleton. Highly phosphorylated forms of tau are deposited in the brain in a range of neurodegenerative disorders including Alzheimer's disease, progressive supranuclear palsy, and frontotemporal lobar degeneration associated with Pick bodies. A key candidate kinase for both physiological and pathological tau phosphorylation is glycogen synthase kinase-3 (GSK-3). Multiple phosphorylation sites have been identified on tau exposed to GSK-3 in vitro and in cells. In this review, we highlight recent data suggesting a role for GSK-3 activity on physiological tau function and on tau dysfunction in neurodegenerative disease.