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

Figure 2

GSK-3β in the regulation of microglial phagocytosis. Microglial phagocytosis has been shown to be enhanced through activation of TLR2/4 pathway. Binding of Aβ to TLR2/4 may result in activation of PI3K signalling eventually leading to inhibition of GSK-3β activation. This in turn shifts the cellular balance towards increase in the production of antiinflammatory cytokines favouring phagocytic microglial phenotype. On the other hand, CD40R-CD40L interaction results in both NF-κB and GSK-3β activation thus increasing proinflammatory cytokine production. This may shift the phenotype of microglial cells being less capable of clearing Aβ.