Mechanisms of Nur77 in Health, Disease, and Therapeutic Potential

Abstract

The orphan nuclear receptor Nur77 (NR4A1) (TR3) (NGFI-B) plays an important role in liver physiology, regulating key processes such as metabolism and inflammation, and impacting the development and management of diseases like non-alcoholic fatty liver disease (NAFLD), fibrosis, and hepatocellular carcinoma. This review provides a comprehensive exploration of Nur77's structure, functions, and mechanisms of action in different organs and diseases, with a particular focus on its roles in liver health and disease. Nur77 acts as both a transcription factor and a cytoplasmic signalling molecule, regulating glucose and lipid metabolism, inflammation, and apoptosis. Recent research highlights Nur77's involvement in liver regeneration and repair, as well as its dual roles in tumour suppression and tumour promotion. Additionally, Nur77 is implicated in different organ-related diseases. These include cardiovascular diseases (cardiac hypertrophy and apoptosis), neurological diseases (affecting neuroprotection and neural injury), and metabolic disorders such as obesity and diabetes. This review explores Nur77's interactions with key signalling pathways and its potential as a therapeutic target. Evidence suggests that pharmacological activation or inhibition of Nur77 could offer new approaches for treating liver fibrosis, metabolic disorders, and liver cancer. However, the context-dependent nature of Nur77's effects presents both opportunities and challenges for drug development. This review seeks to deepen our understanding of Nur77's roles in liver pathophysiology and to identify research gaps for further investigation. By synthesising current knowledge and recent advances, this review contributes to the growing body of literature on Nur77 and provides a foundation for future studies exploring its potential as a therapeutic target in liver diseases.