Nuclear receptors in health and disease - Jan-Åke Gustafsson
Nuclear receptors (NRs) are ligand-activated transcription factors that encompass receptors for steroid hormones as well as receptors acting as sensors of metabolic compounds such as oxysterols and fatty acids. NRs can control intermediary metabolism as well as cellular proliferation and there is a growing appreciation that NRs could be more widely used as targets for treatment of various diseases. We focus our research on the estrogen receptors (ERs) and the liver X receptors (LXRs). Subtypes of these receptors, α and β, are encoded by different genes and ERβ and LXRβ were discovered in our group.
Tissue specific NR knock-outs
Crucial for our research are mouse models with specific deletions of the receptors and we have shown that the subtypes often have distinct and sometimes even opposite roles. The role of ERs is specifically addressed in relation to breast, prostate and colon cancer and a concept of yin and yang has emerged; ERβ having anti-proliferative pro-differentiative effects. An anti-proliferative effect of LXRβ in colon has also been demonstrated. Our recent studies suggest that diseases of the CNS like Parkinson´s disease and ALS may involve a component of aberrant LXRβ signaling. LXRβ is indicated to play a protective role also in the prevention of bone diseases. We have now generated floxed ERα, ERβ, LXRα and LXRβ mice that will be used to knock out the receptors in selected tissues by using the Cre/LoxP system in order to further advance our understanding of these receptors.