Retinoic acid receptor-related orphan receptor alpha (RORα) (RORα)

Retinoic acid receptor-related orphan receptor alpha (RORα) is a member of the nuclear receptor superfamily that functions as a ligand-dependent transcription factor. It plays a critical role in regulating the molecular clock, particularly through the transcriptional activation of BMAL1, thereby influencing circadian rhythms (UniProt P35398). Beyond its role in the biological clock, RORα is essential for cerebellar development, lipid metabolism, and the regulation of inflammatory responses, specifically in the differentiation of Th17 cells (PubMed 20610536). While historically identified as a potential nuclear receptor for melatonin (RZRα), its primary endogenous ligands are now considered to be oxysterols and cholesterol derivatives (PubMed 21666606). RORα is implicated in various pathologies, including metabolic syndrome, autoimmune disorders, and certain cancers, making it a significant therapeutic target. Pharmacological modulation via synthetic agonists or inverse agonists aims to treat conditions like type 2 diabetes and neuroinflammation by fine-tuning the expression of genes involved in glucose production and cytokine release (PubMed 21170040).

Other names

RORARZR-alphaNR1F1Retinoid-related orphan receptor alphaNuclear melatonin receptor

Ligand-dependent transcriptional regulation of target genes through binding to ROR response elements (ROREs) in DNA.