ArticleCell chemical biology2019
Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Xifeng Zhichou decoction mitigates tic disorder on juvenile rats by regulating neuroinflammation and neurotransmitter homeostasis: dual modulation of Nr4a2 and gut microbiota.Chinese medicine · 2026Article
- Development of a Brain-Penetrant Nurr1 Agonist Tool.ChemMedChem · 2026Article
- Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.eLife · 2026Article
- Structural Tuning of Vidofludimus for High-Efficacy NR4A Agonism.Journal of medicinal chemistry · 2026Article
- A Commentary on Dual Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands.Journal of cellular immunology · 2026Article
- Therapeutic role of plant bioactive compounds in atrazine-mediated neurotoxicity.Advances in neurotoxicology · 2026Article
- Review
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Identification and Validation of Inverse Agonists for Nuclear Receptor Subfamily 4 Group A Member 2.ACS omega · 2025Article
- Quantitative chemoproteomics reveals dopamine's protective modification of Tau.Nature chemical biology · 2025Article
- Molecular Determinants of A9 Dopaminergic Neurons.Neuromolecular medicine · 2025Review
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- A Nurr1 Agonist Derived from the Natural Ligand DHI Induces Neuroprotective Gene Expression.Journal of medicinal chemistry · 2025Article
- BRF110, an Orally Active Nurr1-RXRα-Selective Rexinoid, Enhances BDNF Expression without Elevating Triglycerides.Journal of medicinal chemistry · 2025Article
- New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them.Trends in biochemical sciences · 2024Review
- Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing.Communications chemistry · 2024Article
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
- Investigating the Effect of an Anti-Inflammatory Drug in Determining NURR1 Expression and Thus Exploring the Progression of Parkinson's Disease.Physiological research · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Structure-Guided Design of Nurr1 Agonists Derived from the Natural Ligand Dihydroxyindole.Journal of medicinal chemistry · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Nurr1, a nuclear receptor essential for the development, maintenance, and survival of midbrain dopaminergic neurons, is a potential therapeutic target for Parkinson's disease, a neurological disorder characterized by the degeneration of these same neurons. Efforts to identify Nurr1 agonists have been hampered by the recognition that it lacks several classic regulatory elements of nuclear receptor function, including the canonical ligand-binding pocket. Here we report that the dopamine metabolite 5,6-dihydroxyindole (DHI) binds directly to and modulates the activity of Nurr1. Using biophysical assays and X-ray crystallography, we show that DHI binds to the ligand-binding domain within a non-canonical pocket, forming a covalent adduct with Cys566. In cultured cells and zebrafish, DHI stimulates Nurr1 activity, including the transcription of target genes underlying dopamine homeostasis. These findings suggest avenues for developing synthetic Nurr1 ligands to ameliorate the symptoms and progression of Parkinson's disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.