The ability of PPAR ligands to trans-repress or inhibit the activity of transcription factors like NF-κB is thought to be the main mechanism for their anti-inflammatory actions. Both PPAR agonists and NF-κB inhibitors reduce ethanol intake and preference in mice. For example, an inhibitor of NF-κB (caffeic acid phenylethyl ester) reduced ethanol intake and preference in C57BL/6J mice (Harris and Blednov, 2013). A selective inhibitor of IKKβ, which regulates NF-κB activation, reduced ethanol consumption and preference in these mice (Truitt et al., 2013). Furthermore, genes with NF-κB elements were generally upregulated in post-mortem brains from human alcoholics (Okvist et al., 2007). NFKB1, which encodes a 105 kDa Rel-family protein whose full-length form inhibits transcription and is cleaved into the 50 kDa DNA-binding subunit of NF-κB, has been associated with AD (Edenberg et al., 2008). NF-κB regulates the development and function of both innate and adaptive immunity (Boersma and Meffert, 2008), and NF-κB and its signaling pathways have become a focal point for intense drug discovery efforts (Gupta et al., 2010; Karin et al., 2004). NF-κB is a point of convergence
