Another common link between these gene networks could be their implication in neurodegenerative disease and inflammation. In fact, LXRs have emerged as important regulators of the innate and adaptive immune system and inflammation. LXR signalling impacts the development of Alzheimer’s disease pathology and LXRs are promising therapeutic targets for AD treatment because of their ability to affect components of the disease such as cholesterol content, Ab clearance, APP processing, ABCA1, etc.. It has been recently demonstrated that TR and LXR competitively up-regulate the human selective AD indicator1 gene promoter at the transcriptional levels and both receptors share a positive TRE/LXRE. Indeed, BDNF, like LXR, is WY 14643 involved in cholesterol metabolism and in neurodegenerative disease. In hypothyroid pups we report that T3 treatment increases Bdnf mRNA levels. Crupi et al. have also reported that T3 significantly enhanced the post-traumatic brain injury expression of the neuroprotective neurotrophin BDNF, showing a potential anti-inflammatory effect of T3. Further, we observed a significant T3-dependent increase in Ppara mRNA levels in the hypothalamic region. Thus, Ppara is centrally regulated by T3 and may be involved in the central regulation of lipid metabolism. Indeed, it is established that, in the periphery, Ppara is a LXR/TR target, and extensive data establish the importance of PPARa in inflammation. Thus, Ppara may be involved at the central level in inflammation. In addition, synthetic LXR agonists have been shown to have anti-inflammatory features. The anti-inflammatory activities of LXR were described in 2003 using a cutaneous inflammatory mouse model in which activation of LXR by GW3965 or 22-hydroxycholesterol inhibited production of TNFa and IL-1a. Interestingly, it has also been demonstrated that a hyperthyroid state in the rat increases circulating levels of TNF-a by actions exerted at the Kupffer cell level, and this is related to the oxidative stress status established in the liver by T3-dependent calorigenesis. Our results show that T3 also increases Tnfa and Il1 in the hypothalamic region. Thus, the crosstalk between LXR and TH is also involved in central regulation of inflammation. Indeed, those two pathways could act synergistically to reduce inflammation, LXR inhibiting Trh transcription and thus T3 secretion, leading to a subsequent reduction of TNFa and IL1 production, reinforcing the repressive effect of LXR on these two factors. Thus, LXRs could be attractive drug targets for therapeutic intervention in metabolic disorders and inflammatory diseases even at the central level. RXR also plays an important role in the regulation of inflammation. Finally, TRs act also as inhibitors of inflammation. These data together lead us to suggest that it could exist an interaction between TR/RXR and LXR at the central level to regulate inflammation in addition to the metabolism regulation.