ArticleNature chemical biology2020
PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 88 citations in OpenAlex.
- 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
- Amyloid-β and Tau in Alzheimer's disease: pathogenesis, mechanisms, and interplay.Cell death & disease · 2026Review
- Review
- PGE1 Suppresses the Expression of M2 Markers on Macrophages Through Prostaglandin Receptors.Cells · 2025Article
- 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
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- The endocannabinoid anandamide mediates anti-inflammatory effects through activation of NR4A nuclear receptors.British journal of pharmacology · 2025Article
- BRF110, an Orally Active Nurr1-RXRα-Selective Rexinoid, Enhances BDNF Expression without Elevating Triglycerides.Journal of medicinal chemistry · 2025Article
- A Nurr1 Agonist Derived from the Natural Ligand DHI Induces Neuroprotective Gene Expression.Journal of medicinal chemistry · 2025Article
- Early prostaglandin EFrontiers in ophthalmology · 2025Article
- Postmortem Fatty Acid Abnormalities in the Cerebellum of Patients with Essential Tremor.Cerebellum (London, England) · 2024Article
- Review
- 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
- Article
- The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses.Frontiers in pharmacology · 2024Article
- Application of clinical blood metabogram for diagnosis of early-stage Parkinson's disease: a pilot study.Frontiers in molecular biosciences · 2024Article
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 Å resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21° shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.
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Registered trials
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.