Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease

Figure 5

PPARγ receptor (a) is in the repressed state due to the transcriptional cofactor inhibitors NCoR/SMRT binding with PPARγ and preventing the transcription of target genes. When traditional (full agonist, (b)) or selective agonist (c) changes the confirmation of the PPARγ receptor and corepressors NCoR/SMRT come off. Traditional agonists (full agonist) such as rosiglitazone or pioglitazone promote a stable confirmation of the PPARγ-RXR confirmation with coactivators CBP/P300. However, selective agonists can induce an unstable confirmation of the PPARγ complex and allow alternative interactions with nontraditional coactivators, potentially PGC-1α, thus inducing alternative gene expression.