Glycogen synthase kinase 3beta as a target for the therapy of shock and inflammation.
After the discovery that glycogen synthase kinase (GSK) 3beta plays a fundamental role in the regulation of the activity of nuclear factor kappaB, a number of studies have investigated the effects of this protein kinase in the regulation of the inflammatory process. The GSK-3beta inhibition, using genetically modified cells and chemically different pharmacological inhibitors, affects the regulation of various inflammatory mediators in vitro and in vivo. Insulin, an endogenous inhibitor of GSK-3 in the pathway leading to the regulation of glycogen synthase activity, has recently been clinically used in the therapy for septic shock. The beneficial anti-inflammatory effects of insulin in preclinical and clinical studies could possibly be due, at least in part, to the inhibition of GSK-3 and not directly correlated to the regulation of blood glucose. We describe the latest studies describing the effects of GSK-3 inhibition as potential target of the therapy for diseases associated with inflammation, ischemia/reperfusion, and shock.
Dugo
Laura
L
Centre for Experimental Medicine, Nephrology and Critical Care Medicine, William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, UK.
Collin
Marika
M
Thiemermann
Christoph
C
D000818:Animals; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006006:Glycogen Synthase / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D007328:Insulin / Q000627:therapeutic use; D016328:NF-kappa B / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology; D012769:Shock / Q000188:drug therapy / Q000201:enzymology*
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D016328:NF-kappa B; D006006:Glycogen Synthase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3