생화학분자생물학회입니다.
NurrOn: the Nurr1 nuclear receptor deorphanization
작성자
Kwang-Soo Kim작성일자
2021-03-23조회수
256Kwang-Soo Kim ( kskim@mclean.harvard.edu ) | ||
2011-present | Professor and Director, Molecular Neurobiology Lab, McLean Hospital and Program in Neuroscience, Harvard Medical School, USA | |
1998-2010 | Associate Professor and Director, Molecular Neurobiology Lab, McLean Hospital and Program in Neuroscience, Harvard Medical School, USA | |
1994-1998 | Associate Professor, Dept. of Neurology and Dept. of Anatomy and Neurobiology, University of Tennessee, College of Medicine, USA | |
1989-1994 | Assistant Professor, Dept. of Neurology and Neuroscience, Cornell University College of Medicine, USA | |
1983-1988 | Postdoctoral fellow, Department of Biology, MIT, USA |
NurrOn: the Nurr1 nuclear receptor deorphanization
Nurr1 (NR4A2) is critical not only for the development and maintenance of midbrain dopamine neurons but also for their protection from inflammation-induced neuronal death. In addition, Nurr1 is also known to regulate the differentiation of regulatory T cell through activation of Foxp3 and is critical for autoimmune diseases. Hence, compounds that activate Nurr1’s transcription function are of a great interest for understanding and potential treatment of dopamine-related brain disorders and autoimmune diseases. Until recently, Nurr1 has been considered to be a ligand-independent nuclear receptor due to structural studies showing a narrow and tight ligand binding pocket. However, recent studies have identified synthetic compounds that can induce the transcriptional activity of Nurr1, suggesting the existence of native ligands. Indeed, two endogenous ligands were recently identified with co-crystal structure and functional analyses, strongly suggesting that Nurr1 is now an adopted nuclear receptor. In this review, we introduce these novel endogenous and synthetic Nurr1 agonists and discuss their potential to understand and treat Nurr1-related diseases.
Exp Mol Med. 2021 Jan;53(1):19-29. doi: 10.1038/s12276-021-00555-5.
https://www.ncbi.nlm.nih.gov/pubmed/33479411