Review Article

Glycogen Synthase Kinase-3β: A Mediator of Inflammation in Alzheimer's Disease?

Figure 1

GSK-3β regulates the production of microglial inflammatory molecules. GSK-3β activation has been shown to increase the production of proinflammatory mediators via multiple mechanisms. GSK-3β is able to activate JNK-, STAT3/5- and NF-κB pathways leading to increased cytokine and chemokine production. GSK-3β is able to increase the binding of coactivator CREB-binding protein (CBP) to p65 thus enhancing NF-κB mediated transcription. Since CREB competes for CBP binding, activation of GSK-3β shifts the balance in favor of NF-κB pathway and CREB-mediated induction of IL-10 is reduced. Moreover, GSK-3β activation leads to proteosomal degradation of beta-catenin, thus resulting in reduced inhibition of NF-κB-activation. All these events lead to enhanced production of proinflammatory molecules.
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