Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1
Open Access
- 21 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Experimental & Molecular Medicine
- Vol. 53 (1), 19-29
- https://doi.org/10.1038/s12276-021-00555-5
Abstract
Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small molecular ligands to bind. In-depth characterization of its ligand-binding pocket revealed that it is highly dynamic, with its structural conformation changing more than twice on the microsecond-to-millisecond timescale. This observation suggests the possibility that certain ligands are able to squeeze into this narrow space, inducing a conformational change to create an accessible cavity. The cocrystallographic structure of Nurr1 bound to endogenous ligands such as prostaglandin E1/A1 and 5,6-dihydroxyindole contributed to clarifying the crucial roles of Nurr1 and opening new avenues for therapeutic interventions for neurodegenerative and/or inflammatory diseases related to Nurr1. This review introduces novel endogenous and synthetic Nurr1 agonists and discusses their potential effects in Nurr1-related diseases.Keywords
Funding Information
- Hanyang University (201800000003221)
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