Research Progress of GSK3 in the Pathophysiology of Depression Disorder

Abstract

Abstract: Despite many decades of clinical useness, the therapeutic target of lithium remains uncertain.It is recognized that therapeutic concentrations of lithium is to inhibit the activity of glycogen synthase kinase-3 (GSK3) to treat depression disorder. Specifically, it has been demonstrated that lithium administration regulates multiple GSK3 targets and multiple antidepressant drugs regulate GSK3 signaling. Pharmacological and genetic inhibition of GSK3 results in mood stabilizer-like and antidepressant-like behavior in rodent models. These studies implicate that GSK3 is a possible target for treatment of mood disorders. Furthermore, numerous recent studies have provided more complete understanding of the role of GSK3 in diverse neurological processes, strengthening the hypothesis that GSK3 may represent a therapeutically relevant target of lithium. For example, GSK3 is a primary regulator of oxidative stress response. Inflammatory response, neurogenesis, serotonin transmission and circadian rhythms may be involved in GSK3-regulated pathways. In this regard, further study is needed to develop novel specific GSK3 inhibitors for the treatment of depressive disorders. In this article, we will discuss the role of GSK3 in five aspects including oxidative stress response, inflammatory response, neurogenesis, serotonin transmission and circadian rhythms to summary the research progress in pathological mechanisms of depression.

Key words: GSK3 inhibitor, depressive disorders, inflammation, neurogenesis, circadian rhythm

CLC Number:

CHEN Jiao, CHU Shi-feng, WANG Zhen-zhen, CHEN Nai-hong. Research Progress of GSK3 in the Pathophysiology of Depression Disorder[J]. Acta Neuropharmacologica, 2014, 4(5): 44-54.

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