Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders

Abstract

Nur77 belongs to the NR4A subgroup of the nuclear receptor superfamily. Unlike other nuclear receptors, a natural ligand for Nur77 has not been identified yet. However, a few small molecules can interact with this receptor and induce a conformational change to mediate its activity. The expression and activation of Nur77 can be rapidly increased using various physiological and pathological stimuli. In vivo and in vitro studies have demonstrated its regulatory role in tissues and cells of multiple systems by means of participation in cell differentiation, apoptosis, metabolism, mitochondrial homeostasis, and other processes. Although research on Nur77 in the pathophysiology of the central nervous system (CNS) is currently limited, the present data support the fact that Nur77 is involved in many neurological disorders such as stroke, multiple sclerosis, Parkinson's disease. This indicates that activation of Nur77 has considerable potential in treating these diseases. This review summarizes the regulatory mechanisms of Nur77 in CNS diseases and presents available evidence for its potential as targeted therapy, especially for cerebrovascular and inflammationrelated CNS diseases.

Keywords: Nur77; apoptosis; central nervous system; inflammation; multiple sclerosis; stroke.

Fig. (1)

The mechanism of Nur77 regulating cell survival and apoptosis in CNS. Nur77 mediates cell apoptosis through caspase, endoplasmic reticulum stress, and mitochondrial autophagy, while the PI3K/AKT pathway is involved in Nur77-mediated cell survival. (A higher resolution / colour version of this figure is available in the electronic copy of the article).