Glycogen synthase kinase 3, circadian rhythms, and bipolar disorder: a molecular link in the therapeutic action of lithium |
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| Authors: | Sevag A Kaladchibachi Brad Doble Norman Anthopoulos James R Woodgett Armen S Manoukian |
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| Institution: | (1) Division of Signaling Biology, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ont, M5G 2M9, Canada;(2) Stem Cell and Cancer Research Institute, McMaster University, 1200 Main Street, West, Hamilton, Ont, L8N 3Z5, Canada;(3) Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont, M5G 1X5, Canada |
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| Abstract: | Background Bipolar disorder (BPD) is a widespread condition characterized by recurring states of mania and depression. Lithium, a direct
inhibitor of glycogen synthase kinase 3 (GSK3) activity, and a mainstay in BPD therapeutics, has been proposed to target GSK3
as a mechanism of mood stabilization. In addition to mood imbalances, patients with BPD often suffer from circadian disturbances.
GSK3, an essential kinase with widespread roles in development, cell survival, and metabolism has been demonstrated to be
an essential component of the Drosophila circadian clock. We sought to investigate the role of GSK3 in the mammalian clock mechanism, as a possible mediator of lithium's
therapeutic effects. |
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