Glycogen synthase kinase 3 substrates in mood disorders and schizophrenia.

The dominant genetic and environmental causes of mood disorders and schizophrenia have not been forthcoming, so alternative approaches are required to elucidate the mechanisms underlying these diseases and to develop improved treatments for use in the clinic. Pharmacological evidence implicates glycogen synthase kinase 3 (GSK3) as a key target of current therapeutics, and this is well supported by genetic studies in animal models. Several upstream regulators of GSK3 are also genetically associated with mood disorders and schizophrenia, further suggesting convergence on GSK3 signalling. Whereas pathways upstream of GSK3 are being elucidated, relatively little progress has been made in identifying targets downstream of GSK3 that mediate its functional effects. This is important, because these substrates themselves could become next-generation therapeutic targets that are more potent and specific than current therapeutics targeting GSK3. Here, a few likely candidates and their connection to mood disorders and schizophrenia are discussed.