The possible role of the Akt signaling pathway in schizophrenia

Zheng, Wenhua, Wang, Haitao, Zeng, Zhiwen, Lin, Jun, Little, Peter J., Srivastava, Lalit K. and Quirion, Remi (2012) The possible role of the Akt signaling pathway in schizophrenia. Brain Research, 1470 145-158. doi:10.1016/j.brainres.2012.06.032

Author Zheng, Wenhua
Wang, Haitao
Zeng, Zhiwen
Lin, Jun
Little, Peter J.
Srivastava, Lalit K.
Quirion, Remi
Title The possible role of the Akt signaling pathway in schizophrenia
Journal name Brain Research   Check publisher's open access policy
ISSN 0006-8993
Publication date 2012-08-27
Year available 2012
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.brainres.2012.06.032
Open Access Status Not yet assessed
Volume 1470
Start page 145
End page 158
Total pages 14
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Abstract Serine/threonine protein kinase v-akt murine thymoma viral oncogene homolog (Akt) is one of the survival kinases with multiple biological functions in the brain and throughout the body. Schizophrenia is one of the most devastating psychiatric disorders. Accumulating evidence has indicated the involvement of the Akt signaling pathway in the pathogenesis of this disorder. Genetic linkage and association studies have identified Akt-1 as a candidate susceptibility gene related for schizophrenia. The level of Akt-1 protein and its kinase activity decreased significantly both in white blood cells from schizophrenic patients and in postmortem brain tissue of schizophrenic patients. Consistent with these findings, alterations in the upstream and downstream pathways of Akt have also been found in many psychiatric disorders. Furthermore, both typical and atypical antipsychotic drugs modify the Akt signaling pathway in a variety of conditions relative to schizophrenia. In addition as a survival kinase, Akt participates in neurodevelopment, synaptic plasticity, protein synthesis and neurotransmission in the central nervous system. It is thought that reduced activity of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway could at least partially explain the cognitive impairment, synaptic morphologic abnormality, neuronal atrophy and dysfunction of neurotransmitter signaling in schizophrenia. In addition, reduced levels of Akt may increase the effects of risk factors on neurodevelopment, attenuate the effects of growth factors on neurodevelopment and reduce the response of patients to antipsychotic agents. More recently, the role of Akt signaling in the functions of schizophrenia susceptibility genes such as disrupted-in-schizophrenia 1 (DISC-1), neuregulin-1 (NRG-1) and dysbindin-1 has been reported. Thus, Akt deficiency may create a context permissive for the expression of risk-gene effects in neuronal morphology and function. This paper reviews the role of Akt in the pathophysiology of schizophrenia and as a potential therapeutic strategy targeting Akt.
Keyword Akt
Dopamine receptor
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 30670652
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Pharmacy Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 47 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 47 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 13 Jun 2015, 06:37:06 EST by System User on behalf of Learning and Research Services (UQ Library)