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

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.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Gould TD,Picchini AM,Einat H,Manji HK

doi

10.2174/1389450110607011399

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

1399-409

issue

11

eissn

1389-4501

issn

1873-5592

journal_volume

7

pub_type

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