Roles of PI3K/AKT/GSK3 Pathway Involved in Psychiatric Illnesses

被引:159
作者
Matsuda, Satoru [1 ]
Ikeda, Yuka [1 ]
Murakami, Mutsumi [1 ]
Nakagawa, Yukie [1 ]
Tsuji, Ai [1 ]
Kitagishi, Yasuko [1 ]
机构
[1] Nara Womens Univ, Dept Food Sci & Nutr, Kita Uoya Nishimachi, Nara 6308506, Japan
关键词
PI3K; AKT; GSK3; PTEN; cell signaling; schizophrenia; depression;
D O I
10.3390/diseases7010022
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Psychiatric illnesses may be qualified to the cellular impairments of the function for survival or death in neurons, which may consequently appear as abnormalities in the neuroplasticity. The molecular mechanism has not been well understood, however, it seems that PI3K, AKT, GSK3, and their downstream molecules have crucial roles in the pathogenesis. Through transducing cell surviving signal, the PI3K/AKT/GSK3 pathway may organize an intracellular central network for the action of the synaptic neuroplasticity. In addition, the pathways may also regulate cell proliferation, cell migration, and apoptosis. Several lines of evidence have supported a role for this signaling network underlying the development and treatment for psychiatric illnesses. Indeed, the discovery of molecular biochemical phenotypes would represent a breakthrough in the research for effective treatment. In this review, we summarize advances on the involvement of the PI3K/AKT/GSK3 pathways in cell signaling of neuronal cells. This study may provide novel insights on the mechanism of mental disorder involved in psychiatric illnesses and would open future opportunity for contributions suggesting new targets for diagnostic and/or therapeutic procedures.
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页数:11
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共 74 条
[1]   Structural Basis for Ligand Regulation of the Fatty Acid-binding Protein 5, Peroxisome Proliferator-activated Receptor β/δ (FABP5-PPAR β/δ) Signaling Pathway [J].
Armstrong, Eric H. ;
Goswami, Devrishi ;
Griffin, Patrick R. ;
Noy, Noa ;
Ortlund, Eric A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (21) :14941-14954
[2]   The Antiproliferative Response of Indole-3-Carbinol in Human Melanoma Cells Is Triggered by an Interaction with NEDD4-1 and Disruption of Wild-Type PTEN Degradation [J].
Aronchik, Ida ;
Kundu, Aishwarya ;
Quirit, Jeanne G. ;
Firestone, Gary L. .
MOLECULAR CANCER RESEARCH, 2014, 12 (11) :1621-1634
[3]   Systematic review and meta-analysis of omega-3-fatty acids in elderly patients with depression [J].
Bae, Ji-Hyun ;
Kim, Gaeun .
NUTRITION RESEARCH, 2018, 50 :1-9
[4]   Akt1 deficiency in schizophrenia and impairment of hippocampal plasticity and function [J].
Balu, Darrick T. ;
Carlson, Gregory C. ;
Talbot, Konrad ;
Kazi, Hala ;
Hill-Smith, Tiffany E. ;
Easton, Rachel M. ;
Birnbaum, Morris J. ;
Lucki, Irwin .
HIPPOCAMPUS, 2012, 22 (02) :230-240
[5]   Brief exposure to obesogenic diet disrupts brain dopamine networks [J].
Barry, Robert L. ;
Byun, Nellie E. ;
Williams, Jason M. ;
Siuta, Michael A. ;
Tantawy, Mohammed N. ;
Speed, Nicole K. ;
Saunders, Christine ;
Galli, Aurelio ;
Niswender, Kevin D. ;
Avison, Malcolm J. .
PLOS ONE, 2018, 13 (04)
[6]   Nuclear PTEN Controls DNA Repair and Sensitivity to Genotoxic Stress [J].
Bassi, C. ;
Ho, J. ;
Srikumar, T. ;
Dowling, R. J. O. ;
Gorrini, C. ;
Miller, S. J. ;
Mak, T. W. ;
Neel, B. G. ;
Raught, B. ;
Stambolic, V. .
SCIENCE, 2013, 341 (6144) :395-399
[7]   A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health [J].
Beaulieu, Jean-Martin .
JOURNAL OF PSYCHIATRY & NEUROSCIENCE, 2012, 37 (01) :7-16
[8]   An Akt/β-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior [J].
Beaulieu, JM ;
Sotnikova, TD ;
Marion, S ;
Lefkowitz, RJ ;
Gainetdinov, RR ;
Caron, MG .
CELL, 2005, 122 (02) :261-273
[9]   Genetic Deletion of Akt3 Induces an Endophenotype Reminiscent of Psychiatric Manifestations in Mice [J].
Bergeron, Yan ;
Bureau, Genevieve ;
Laurier-Laurin, Marie-Elaine ;
Asselin, Eric ;
Massicotte, Guy ;
Cyr, Michel .
FRONTIERS IN MOLECULAR NEUROSCIENCE, 2017, 10
[10]   GSK3 activity regulates rhythms in hippocampal clock gene expression and synaptic plasticity [J].
Besing, Rachel C. ;
Rogers, Courtney O. ;
Paul, Jodi R. ;
Hablitz, Lauren M. ;
Johnson, Russell L. ;
McMahon, Lori L. ;
Gamble, Karen L. .
HIPPOCAMPUS, 2017, 27 (08) :890-898