Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease

Figure 4

PPARγ agonist mediated transrepression of NF-kB signaling. Activation of PPARγ occurs upon binding of PPARγ agonists through association of heterodimer with coactivator complex to form a transcriptional complex. This complex binds to the PPARγ response element (PPRE) of IkBα gene, thereby inducing the expression of IkBα. An additional transrepressive mechanism involves inhibition of IKKα/β, an upstream kinase of IkBα. Consequently, degradation of IkBα and subsequent nuclear-translocation and activation of NF-kB (p50/p65) fail to occur, resulting in inhibition of inflammatory gene expression.