The multiple mechanisms of NR4A2 in neurological disorders and advances in targeted therapy research

Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) is a transcription factor widely distributed in the central nervous system, playing a crucial regulatory role in various physiological and pathological processes, including dopaminergic neuronal differentiation, synaptic plasticity, neuroinflammation, immune responses, and addictive behaviors. Previous studies have primarily focused on exploring the relationship between NR4A2 and Parkinson's disease, with less attention given to the potential association between NR4A2 and other neurological disorders. In this context, this paper systematically reviews the current research on NR4A2 in Parkinson's disease, Alzheimer's disease, multiple sclerosis, psychiatric disorders, neurodevelopmental disorders (NDD), addictive behaviors, and stroke, revealing its multifaceted mechanisms in neurological disorders and elucidate its common and specific roles across different conditions. Furthermore, it also highlights cutting-edge strategies such as NR4A2 agonists, indirect NR4A2 regulators, and NR4A2-based cell replacement therapy or gene therapy, providing a comprehensive discussion of the progress and breakthroughs in NR4A2-targeted therapeutic approaches.