RXRs are essential for PPAR signaling. Specifically, RXRs heterodimerize with PPARs, creating ‘permissive’ signaling complexes that increase expression of PPAR target genes following ligation with either a RXR-specific agonist or a PPAR partner ligand (Mangelsdorf and Evans, 1995; Szanto et al., 2004). There are three RXR isotypes: RXRα, RXRβ and RXRγ. In the intact CNS, neurons and glia constitutively express RXRs (Schrage et al., 2006). In injury or disease, the subcellular location of RXR switches from the cytoplasm to the nucleus, suggesting transcriptional activation of RXR-containing heterodimers (Schrage et al., 2006). Known ligands for RXRs include honokiol (a naturally occurring ligand from the bark of the magnolia tree), the synthetic agonist Bexarotene (Targretin), and 9-cis retinoic acid (Qu and Tang, 2010; Kotani et al., 2010). Considering that Bexarotene is already FDA-approved and has an excellent side-effect profile, it is an optimal candidate for translational studies on neurodegenerative diseases or injuries (Lansigan and Foss, 2010).
