Anti-inflammatory Potential of GSK-3 Inhibitors

: Glycogen synthase kinase -3 (GSK-3) is a protein kinase containing threonine or serine amino acid residues. GSK-3 was first discovered in 1980 as a regulatory protein kinase for its namesake, Glycogen synthase (GS) enzyme, which is responsible for the conversion of glycogen from glucose with the help of uridine diphosphate glucose (UDP-Glu) residue. GSK-3 has two isoforms present in human’s beings namely GSK-3 α (serine residue at 21 position) and GSK-3 β (serine residue at 9 position). GSK-3 has two terminals namely C- terminal and N- terminal. C-terminal of GSK-3 looks like α- helix conformation which acts as activator loop and is responsible for helping to position residues like symphoric effect involved in ATP binding and catalysis of substrates. On the other hand, the N- terminal of GSK-3 is like β- strand conformation which acts as an inhibitory loop, and having tyrosine molecule at 216 positions essential for showing the complete GSK-3 activity. N- terminal of GSK-3 is responsible for ATP binding activity and exhibits various biological activities like cell signaling, gene induction following activation of T cell receptor, apoptosis, protein translation, glycogen metabolism, and inflammatory process. Activation of GSK-3 causes Pro- inflammatory actions, increase the binding activity of NF-kB (pro-inflammatory genes), increase the transactivation activity of NF-kB, Increase the phosphorylation of p105, decrease the transactivation activity of C/EBPβ (anti-inflammatory genes) resulting in a large number of prevalent diseases such as diabetes, cancer, neurodegenerative diseases, psychiatric diseases, mood disorders, etc. Glycogen synthase kinase inhibitors (GSK-3 inhibitors) are various chemotypes and have a different mechanism of actions. They are obtained from different sources such as natural products, synthetic ATP as well as non-ATP competitive inhibitors along with substratecompetitive inhibitors. The inhibitors of GSK3 proved to be providing very potent anti-inflammatory action. GSK-3 inhibitors are useful in treating different prevalent disorders, such as neurodegenerative diseases including Alzheimer's disease, hyperglycemia, cancer disease, and mood disorders like depression, etc. In this review, we have highlighted the views regarding the description and types of GSK, inflammation process, and the factors affecting inflammation, the relationship between inflammation and GSK, GSK3 inhibitors, and finally, the reflection of various natural as well as synthetic GSK3 inhibitors having anti-inflammatory activity.