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The possible role of the Akt signaling pathway in schizophrenia
Zheng, WH1,2; Wang, HT2; Zeng, ZW2; Lin, J3; Little, PJ4,5; Srivastava, LK6; Quirion, R6
2012
Source PublicationBRAIN RESEARCH
ISSN1872-6240
Volume1470Pages:145-158
Abstract

Serine/threonine protein kinase v-akt murine thymoma viral oncogene homolog (Akt) is one of thesurvival 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. Inaddition 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 ofphosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway could at least partially explain thecognitive impairment, synaptic morphologic abnormality, neuronal atrophy and dysfunction ofneurotransmitter signaling in schizophrenia. In addition, reduced levels of Akt may increase theeffects of risk factors on neurodevelopment, attenuate the effects of growth factors on neurodevelopment and reduce the response of patients to antipsychotic agents. More recently, therole 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, Aktdeficiency 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 schizophreniaand as a potential therapeutic strategy targeting Akt. (C) 2012 Elsevier B.V. All rights reserved.

KeywordAkt Antipsychotic Schizophrenia Dopamine Receptor Neurodevelopment
DOIhttps://dx.doi.org/10.1016/j.brainres.2012.06.032
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000308679500016
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Cited Times [WOS]:67   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510006, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
3.Suny Downstate Med Ctr, Dept Anesthesiol, Brooklyn, NY 11203 USA
4.RMIT Univ, Discipline Pharm, Sch Med Sci, Bundoora, Vic 3083, Australia
5.RMIT Univ, Diabet Complicat Grp, Hlth Innovat Res Inst, Bundoora, Vic 3083, Australia
6.McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada
Recommended Citation
GB/T 7714
Zheng, WH,Wang, HT,Zeng, ZW,et al. The possible role of the Akt signaling pathway in schizophrenia[J]. BRAIN RESEARCH,2012,1470:145-158.
APA Zheng, WH.,Wang, HT.,Zeng, ZW.,Lin, J.,Little, PJ.,...&Quirion, R.(2012).The possible role of the Akt signaling pathway in schizophrenia.BRAIN RESEARCH,1470,145-158.
MLA Zheng, WH,et al."The possible role of the Akt signaling pathway in schizophrenia".BRAIN RESEARCH 1470(2012):145-158.
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