GLYCOGEN SYNTHASE KINASE 3β AS A TARGET FOR THE THERAPY OF SHOCK AND INFLAMMATION

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Abstract

ABSTRACT

After the discovery that glycogen synthase kinase (GSK) 3β plays a fundamental role in the regulation of the activity of nuclear factor κB, a number of studies have investigated the effects of this protein kinase in the regulation of the inflammatory process. The GSK-3β 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.

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