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International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 479249, 12 pages
Review Article

Deconstructing GSK-3: The Fine Regulation of Its Activity

1NOSCIRA S.A., Tres Cantos, 28760 Madrid, Spain
2Centro de Biología Molecular “Severo Ochoa,” CSIC-UAM-CIBERNED Nicolás Cabrera 1, 28049 Madrid, Spain

Received 21 February 2011; Accepted 28 February 2011

Academic Editor: Peter Crouch

Copyright © 2011 Miguel Medina and Francisco Wandosell. 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.


Glycogen synthase kinase-3 (GSK-3) unique position in modulating the function of a diverse series of proteins in combination with its association with a wide variety of human disorders has attracted significant attention to the protein both as a therapeutic target and as a means to understand the molecular basis of these disorders. GSK-3 is ubiquitously expressed and, unusually, constitutively active in resting, unstimulated cells. In mammals, GSK-3α and β are each expressed widely at both the RNA and protein levels although some tissues show preferential levels of some of the two proteins. Neither gene appears to be acutely regulated at the transcriptional level, whereas the proteins are controlled posttranslationally, largely through protein-protein interactions or by posttranslational regulation. Control of GSK-3 activity thus occurs by complex mechanisms that are each dependent upon specific signalling pathways. Furthermore, GSK-3 appears to be a cellular nexus, integrating several signalling systems, including several second messengers and a wide selection of cellular stimulants. This paper will focus on the different ways to control GSK-3 activity (phosphorylation, protein complex formation, truncation, subcellular localization, etc.), the main signalling pathways involved in its control, and its pathological deregulation.