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The role of glycogen synthase kinase-3beta in schizophrenia.
Drug News Perspect. 2007 Sep; 20(7):437-45.DN

Abstract

Glycogen synthase kinase (GSK)-3beta is recognized as a ubiquitous multifunctional enzyme involved in the modulation of many aspects of neuronal function. Inhibitory control of GSK-3beta has been identified to be crucial for the phosphoinositide 3'-kinase (PI3K)-protein kinase B (Akt)-mediated cell survival. Several lines of evidence converge in implicating abnormal GSK-3beta activity in the pathogenesis of schizophrenia. Preclinical evidence showing that both typical and atypical antipsychotics can indirectly inhibit the activity of GSK-3beta, has pointed to GSK-3beta as a possible therapeutic target for schizophrenia. It is well known that GSK-3beta can be indirectly inhibited via regulation of several intracellular signaling cascades, including the canonical Wnt, Reelin and tyrosine kinase receptor (Trk)-PI3K-Akt. Recently, direct inhibition of GSK-3beta has emerged as a possible option in the pharmacotherapy of several neuropsychiatric disorders. There is, however, a number of issues that need to be considered regarding therapeutic utility of GSK-3beta inhibitors. This article reviews the evidence supporting the possible role of aberrant GSK-3beta in the pathogenesis of schizophrenia and thus suggesting GSK-3beta to be a potential therapeutic target for this disorder.

Authors+Show Affiliations

Department of CNS Research, Boehringer-Ingelheim Pharma GmbH & Co., Biberach, Germany. eliza.koros@boehringer-ingelheim.comNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17992266

Citation

Koros, Eliza, and Cornelia Dorner-Ciossek. "The Role of Glycogen Synthase Kinase-3beta in Schizophrenia." Drug News & Perspectives, vol. 20, no. 7, 2007, pp. 437-45.
Koros E, Dorner-Ciossek C. The role of glycogen synthase kinase-3beta in schizophrenia. Drug News Perspect. 2007;20(7):437-45.
Koros, E., & Dorner-Ciossek, C. (2007). The role of glycogen synthase kinase-3beta in schizophrenia. Drug News & Perspectives, 20(7), 437-45.
Koros E, Dorner-Ciossek C. The Role of Glycogen Synthase Kinase-3beta in Schizophrenia. Drug News Perspect. 2007;20(7):437-45. PubMed PMID: 17992266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of glycogen synthase kinase-3beta in schizophrenia. AU - Koros,Eliza, AU - Dorner-Ciossek,Cornelia, PY - 2007/11/10/pubmed PY - 2007/12/28/medline PY - 2007/11/10/entrez SP - 437 EP - 45 JF - Drug news & perspectives JO - Drug News Perspect VL - 20 IS - 7 N2 - Glycogen synthase kinase (GSK)-3beta is recognized as a ubiquitous multifunctional enzyme involved in the modulation of many aspects of neuronal function. Inhibitory control of GSK-3beta has been identified to be crucial for the phosphoinositide 3'-kinase (PI3K)-protein kinase B (Akt)-mediated cell survival. Several lines of evidence converge in implicating abnormal GSK-3beta activity in the pathogenesis of schizophrenia. Preclinical evidence showing that both typical and atypical antipsychotics can indirectly inhibit the activity of GSK-3beta, has pointed to GSK-3beta as a possible therapeutic target for schizophrenia. It is well known that GSK-3beta can be indirectly inhibited via regulation of several intracellular signaling cascades, including the canonical Wnt, Reelin and tyrosine kinase receptor (Trk)-PI3K-Akt. Recently, direct inhibition of GSK-3beta has emerged as a possible option in the pharmacotherapy of several neuropsychiatric disorders. There is, however, a number of issues that need to be considered regarding therapeutic utility of GSK-3beta inhibitors. This article reviews the evidence supporting the possible role of aberrant GSK-3beta in the pathogenesis of schizophrenia and thus suggesting GSK-3beta to be a potential therapeutic target for this disorder. SN - 0214-0934 UR - https://www.unboundmedicine.com/medline/citation/17992266/The_role_of_glycogen_synthase_kinase_3beta_in_schizophrenia_ L2 - http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=3&p_RefId=1149632 DB - PRIME DP - Unbound Medicine ER -