Nongenomic Actions of Retinoids: Role of Nur77 and RXR in the Regulation of Apoptosis and Inflammation

Recent advances have suggested that nongenomic action of retinoids and their receptors represents an important mechanism by which they exert therapeutic effects. Here we review rapid biological responses triggered by retinoids and related molecules by focusing on novel nongenomic mechanisms involving cytoplasmic action of nuclear receptors Nur77 and retinoid X receptor (RXR) in the regulation of apoptosis and inflammation. A class of apoptosis-inducing compounds related to atypical retinoid AHPN/CD437 has emerged as promising therapeutic agents. They rapidly induce mitochondrial targeting of Nur77 and RXR and conversion of Bcl-2 from a cellular protector to a killer. Thus, understanding the nongenomic action of Nur77 and RXR may provide a rational basis to guide the design and development of new therapeutic agents for cancer, and skin, cardiovascular, metabolic and central nervous disorders.