Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase encoded by two genes in mammals, GSK-3α and GSK-3β [8]. These genes could be found in all eukaryotic cells. GSK-3 phosphorylates its substrate at the site of serine or threonine and inhibits the activity of its downstream targets [1; 9; 10]. GSK-3 was discovered initially as an inhibitor of glycogen synthase [2]. Then, it was found that GSK-3 was also relevant to regulate immune and migratory processes. The immune response activity of CD4+ T cell could be suppressed by inactivating of GSK-3β gene [6]. Furthermore, for the reason that GSK3 could promote the production of inflammatory molecules and initiate cell migration [4], GSK-3 might be a potential target for the treatment of inflammation. GSK-3 is also known to relate to many signaling pathways on cell proliferation and apoptosis. It was evidenced that GSK-3 is a vital member of Wnt cascade [5], which is a canonical pathway related to cell proliferation. As to the effect of GSK-3 on apoptosis, it could both activate the pro-apoptosis factors p53 and inactivate the survival-promoting factors through its capability of phosphorylation [3; 7]. In addition, GSK-3 plays important roles in the differentiation, cell fate determination and spatial patterning to establish bilateral embryonic symmetry in normal conditions. Recently, GSK-3 was found to be related to some serious diseases, such as Alzheimer’s disease and cancer. In a word, GSK-3 carries significant responsibility in regulating physiological function. Thus, with the developing of novel GSK-3 inhibitors, it’s possibly to reach new therapies for GSK-3 related diseases.
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[5] Mills CN, Nowsheen S, Bonner JA, Yang ES. Emerging roles of glycogen synthase kinase 3 in the treatment of brain tumors. Front Mol Neurosci 2011;4:47.
[6] Wang H, Brown J, Martin M. Glycogen synthase kinase 3: a point of convergence for the host inflammatory response. Cytokine 2011;53(2):130-140.
