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Curr Drug Targets. 2006 Nov;7(11):1399-409.

Targeting glycogen synthase kinase-3 in the CNS: implications for the development of new treatments for mood disorders.

Author information

1
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, NIH, Bethesda, MD 20892-3711, USA. gouldt@mail.nih.gov

Abstract

There exists an immediate need to develop novel medications for the treatment of mood disorders such as bipolar disorder and depression. Initial interest in glycogen synthase kinase-3 (GSK-3) as a target for the treatment of mood disorders arose from the finding that the mood stabilizing drug lithium directly inhibited the enzyme. More recent preclinical evidence implicates the modulation of GSK-3 in either the direct or downstream mechanism of action of many other mood stabilizer and antidepressant medications currently in use. One of the cellular targets of GSK-3, which may mediate some of the effects of lithium and other drugs, is beta-catenin, a transcription factor that is rapidly degraded when GSK-3 is active. Recent rodent behavioral data (both genetic and pharmacological) supports GSK-3 representing a therapeutically relevant target of lithium. This includes antidepressant-like behavior in the forced swim test and antimanic-like response to amphetamine following administration of the GSK-3 inhibitor AR-A014418, a findings that is concomitant with an increase in brain beta-catenin. The evidence described in this review suggests that regulating GSK-3 may represent a target for novel medications to treat mood disorders.

PMID:
17100580
DOI:
10.2174/1389450110607011399
[Indexed for MEDLINE]

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