Medicinal Chemistry and Chemical Biology of Nurr1 Modulators: An Emerging Strategy in Neurodegeneration

Nuclear receptor related 1 (Nurr1) is a transcription factor with neuroprotective and antineuroinflammatory properties. Observations from genetic studies and human patients support potential of Nurr1 as a therapeutic target in neurodegeneration, but due to a lack of high-quality chemical tools for pharmacological control of Nurr1, its target validation is pending. Nevertheless, considerable progress has recently been made in elucidating structural and functional characteristics of Nurr1, and several ligand scaffolds have been discovered. Here, we analyze Nurr1’s structure and mechanisms compared to other nuclear receptors, summarize the known small molecule Nurr1 ligands, and discuss the available evidence for the therapeutic potential of Nurr1 in neurodegeneration.