PPARs form obligate heterodimers with RXRs (retinoid X receptors), and ligand binding to either PPAR or RXR initiates gene transcription. PPAR–RXR heterodimers are termed ‘permissive’ because ligation of either component of the heterodimer can induce transcriptional activation of the receptor complex. This means that PPAR activation can be induced to varying degrees by ligands activating RXRs. Since the precise mechanisms by which RXR ligands affect PPAR signaling are not yet defined, it is important to note that RXR activation may not be identical with direct PPAR activation. Currently, FDA-approved agonists of PPARα and PPARγ are used to treat hyperlipidemia and Type II diabetes, respectively (Table 1). These same drugs are also ideal candidates for translational research in models of CNS trauma and disease (Lehmann et al., 1995; Staels et al., 1998).
