Bipolar Research Today is a free monthly online journal that collates and summarizes the latest research about Bipolar, including details on bipolar disorder, symptoms, treatment, depression, medication.

Glycogen synthase kinase-3 in insulin and Wnt signalling: a double-edged sword?

Patel S, Doble B, Woodgett JR

Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.

Glycogen synthase kinase-3 is an unusual protein serine/threonine kinase that, unlike most of its 500-odd relatives in the genome, is active under resting conditions and is inactivated upon cell stimulation. The two mammalian isoforms, GSK-3alpha and beta, play largely overlapping roles and have been implicated in a variety of human pathologies, including Type II diabetes, Alzheimer's disease, bipolar disorder and cancer. Recently, the modes of regulation of this enzyme have been elucidated through a combination of structural and cell biological studies. A series of relatively selective small molecules have facilitated chemical manipulation of the enzyme in intact cells and tissues, and new roles for the protein kinase in embryonic stem cell differentiation and motility have emerged. Despite these advances, the therapeutic value of this enzyme as a drug target remains clouded by uncertainty over the potential of antagonists to promote tumorigenesis. This article describes the state of understanding of this intriguing enzyme, and weighs current evidence regarding whether there is a therapeutic window for amelioration of diseases in which it is implicated, in the absence of inducing new pathologies.

Published 20 October 2004 in Biochem Soc Trans, 32: 803-8.
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