Using Small Molecule GSK3 beta Inhibitors to Treat Inflammation

作者：Klamer G^*; Song E; Ko K H; O'Brien T A; Dolnikov A

来源：Current Medicinal Chemistry, 2010, 17(26): 2873-2881.

• GSK3 beta
• Glycogen synthase kinase 3 beta
• inflammation
• T cells
• immune system

Glycogen Synthase Kinase 3 beta (GSK3 beta) is a serine-threonine kinase originally identified for its role in the conversion of glucose to glycogen. Pharmacological inhibition can be achieved by drug binding to ATP or magnesium binding sites on the enzyme. Pharmaceutical companies have developed several small molecule GSK3 beta inhibitors for diabetes research. Additionally, GSK3 beta inhibitors are being clinically tested as therapeutics for neurological diseases, however, the mechanisms of involvement are unclear. Several studies have shown that the therapeutic effect of GSK3 beta inhibition is associated with the inhibition of inflammation. Similarly, the mechanisms underlying the anti-inflammatory function of GSK3 beta inhibition are not well understood. GSK3 beta inhibition attenuates activation of the pro-inflammatory transcription factor NF kappa B, and activates the immuno-modulatory transcription factor beta-catenin. GSK3 beta inhibition has also been shown to induce secretion of the anti-inflammatory cytokine IL-10. In addition, pharmacological inhibition of GSK3 beta suppressed alloreactive T-cell responses. The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors of GSK3 beta make them an attractive treatment modality towards the control of inflammation.

• 出版日期2010-9