Abstract:

Today a growing body of evidence has directed much attention to the hyperactivation of glycogen synthase kinase-3 (GSK-3) in several psychiatric disorders including schizophrenia and mood disorders. Regulatory mechanisms of GSK-3 activation have become important issues since GSK-3, a member of serine/threonine kinase family, is identified to have numerous roles in intracellular functions by its effect on regulation of at least fifty protein substrates. Among these, particularly the inhibitory control of GSK-3 by Akt is considered as one of the most intriguing mechanisms in psychiatric manner. Hence, in schizophrenia and depression, disruption of Akt-mediated regulation of GSK-3 via two distinct pathways is resulted in hyperactivated GSK-3. In the present study, alterations of two Akt-mediated regulatory mechanisms of GSK-3; phosphoinositide-3 kinase (PI3K) and ß-arrestin complex mediated pathways are reviewed in depression and schizophrenia respectively, and how these alterations reflect GSK-3 activity and consequently contribute to the development of these conditions. Finally the importance of regulatory mechanisms on GSK-3 is highlighted through the aspect of Akt-GSK-3 engagement by possibly bringing novel aspects to the treatments of these disorders. Key words: Akt, GSK-3, PI3K, ß-arrestin, depression, schizophrenia

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