Activating PPARs may also enhance oligodendrocyte survival in the injured or diseased CNS. Oligodendrocytes express all three PPAR isoforms and PPAR activation promotes differentiation and myelin gene expression (Granneman et al., 1998; Saluja et al., 2001; Roth et al., 2003; Woods et al., 2003; Jana et al., 2012). Indeed, genes for many of the myelin proteins contain PPAR response elements indicating they can be directly targeted by PPARs (Jana et al., 2012). For example, the PPARα agonist gemfibrozil stimulates expression of the myelin genes MBP (myelin basic protein), MOG (myelin oligodendrocyte glycoprotein), PLP (proteolipid protein) and CNPase. Using chromatin immunoprecipitation assays, it is possible to show that gemfibrozil enhances binding of PPARδ rather than PPARα, its receptor target, to promoters of myelin genes in human oligodendrocytes (Jana et al., 2012). Moreover, activation of PPARδ promotes myelin protein expression (Saluja et al., 2001).
