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Depression Research and Treatment
Volume 2012 (2012), Article ID 752563, 8 pages
Review Article

Roles of PI3K/AKT/GSK3/mTOR Pathway in Cell Signaling of Mental Illnesses

1Department of Environmental Health Science, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
2Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan

Received 3 August 2012; Revised 9 November 2012; Accepted 21 November 2012

Academic Editor: Michael Maes

Copyright © 2012 Yasuko Kitagishi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several pharmacological agents acting on monoamine neurotransmission are used for the management of mental illnesses. Regulation of PI3K/AKT and GSK3 pathways may constitute an important signaling center in the subcellular integration of the synaptic neurotransmission. The pathways also modulate neuronal cell proliferation, migration, and plasticity. There are evidences to suggest that inflammation of neuron contributes to the pathology of depression. Inflammatory activation of neuron contributes to the loss of glial elements, which are consistent with pathological findings characterizing the depression. A mechanism of anti-inflammatory reactions from antidepressant medications has been found to be associated with an enhancement of heme oxygenase-1 expression. This induction in brain is also important in neuroprotection and neuroplasticity. As enzymes involved in cell survival and neuroplasticity are relevant to neurotrophic factor dysregulation, the PI3K/AKT/GSK3 may provide an important signaling for the neuroprotection in depression. In this paper, we summarize advances on the involvement of the PI3K/AKT/GSK3 pathways in cell signaling of neuronal cells in mental illnesses.