Family reunion of nuclear hormone receptors: structures, diseases, and drug discovery

Hormones comprise one of the most effective classes of messengers that transmit cell to cell communication in eukaryotic systems. Cells receive messages of hormones through protein receptors, and then translate the hormone signals into concrete action of physiological responses. Homeostasis of hormone systems is essential for human health, and aberrant regulation of hormone signaling has been associated with many diseases, including cancer, diabetes, and inflammation diseases. As such, targeting hormone signaling pathways has become a major venue of pharmacological intervention of many health abnormalities. There are two major classes of hormone receptors: G-protein coupled receptors and nuclear hormone receptors, both of which consist of the top two classes of the most successful drug targets. Two years ago, we published a special issue on structures, biology and drug discovery of G-protein coupled receptors, which has been well received by drug discovery research communities. This year marked the 30th anniversary of the cloning of the first member of the nuclear receptor family and 25th year of the discovery of orphan nuclear receptors, for which no cognate ligands were known at the time of their cloning. Since then we have witnessed a tremendous expansion of our knowledge of this family of receptors. In this special issue, we collected eleven exciting review articles, highlighting our current understanding of structure, function, disease relevance, and drug discovery of nuclear receptors.