Activation of RXR elicits a response similar to that observed after PPAR activation. For instance, RXR activation promotes an anti-inflammatory milieu by down-regulating inflammatory signaling in microglia and astrocytes (Xu and Drew, 2006). It also can initiate oligodendrocyte progenitor proliferation, differentiation and myelination (Chao et al., 2010; Nunez et al., 2010; Huang et al., 2011; Kaushik et al., 2012). Interestingly, transcripts for all RXRs are highly up-regulated in demyelinated lesions, with the RXRγ isoform being the highest of the three (Huang et al., 2011). Furthermore, 9-cis retinoic acid enhances OPC differentiation in culture and increases remyelination in cerebellar slice cultures (Huang et al., 2011). Thus, RXR activation could be therapeutic in demyelinating diseases. Additionally, their enhanced ability to readily cross the blood–brain barrier, compared with popular PPAR agonists, makes RXR agonists attractive candidates for the treatment of neurologic diseases (Cramer et al., 2012).
