Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

Abstract

Deciphering what governs inflammation and its effects on tissues is vital for understanding many pathologies. The recent discovery that glycogen synthase kinase-3 (GSK3) promotes inflammation reveals a new component of its well-documented actions in several prevalent diseases which involve inflammation, including mood disorders, Alzheimer's disease, diabetes, and cancer. Involvement in such disparate conditions stems from the widespread influences of GSK3 on many cellular functions, with this review focusing on its regulation of inflammatory processes. GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation, while GSK3 inhibition provides protection from inflammatory conditions in animal models. The involvement of GSK3 and inflammation in these diseases are highlighted. Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions.

14-3-3 Proteins regulate Akt Thr308 phosphorylation in intestinal epithelial cells

“…Moreover, Akt activation augments as revealed by the presence of the active form of Akt (phospho-Akt Thr308; pAkt308) ( Figure 1a). 1 Increased Akt activation was accompanied by phosphorylation of its downstream targets β-catenin ser552 (pβ-cat552) 20 and GSK3β Ser9 (pGSK3β) 21 ( Figure 1a). Augmented Akt1 levels were also detected in the mucosa of inflamed mice, but no changes in total β-catenin and GSK3β were observed (Figure 1a).…”

Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

“…First, we demonstrated that GSK3b plays a crucial role in apoptosis of osteoblasts caused by GC. In osteoblasts, GSK3b is not only the main actor in osteoblastogenesis [5], but also a multi-tasking regulator in many biological events, including structure, gene expression, mobility, and apoptosis [29,30]. Activation of GSK3b is regulated by serine and tyrosine phosphorylation, by protein complex formation, and by its intracellular localization [22].…”

The Pivotal Roles of GSK3β in Glioma Biology

“…Indeed, the activity of GSK3 has been reported in type II diabetes mellitus and obese animal models (Eldar-Finkelman et al, 1999;Nikoulina et al, 2000). GSK3 is also involved in inflammation that accompanies various kinds of diseases (reviewed in Jope et al, 2007). GSK3 inhibition attenuates activation of the pro-inflammatory transcription factor NF-κB and activates the immunomodulatory transcription factor -catenin (Gong et al, 2008).…”