ArticleeLife2023
Molecular basis of ligand-dependent Nurr1-RXRα activation.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pooled it
- Retinoid-X receptor action and disruption in development.Developmental biology · 2026Review
- 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
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Molecular Screening Reveals De Novo Loss-of-FunctionInternational journal of molecular sciences · 2025Article
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- BRF110, an Orally Active Nurr1-RXRα-Selective Rexinoid, Enhances BDNF Expression without Elevating Triglycerides.Journal of medicinal chemistry · 2025Article
- Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing.Communications chemistry · 2024Article
- Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential.Frontiers in pharmacology · 2024Review
- Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology.International journal of molecular sciences · 2023Review
- Alternative activation.eLife · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Small molecule compounds that activate transcription of Nurr1-retinoid X receptor alpha (RXRα) (NR4A2-NR2B1) nuclear receptor heterodimers are implicated in the treatment of neurodegenerative disorders, but function through poorly understood mechanisms. Here, we show that RXRα ligands activate Nurr1-RXRα through a mechanism that involves ligand-binding domain (LBD) heterodimer protein-protein interaction (PPI) inhibition, a paradigm distinct from classical pharmacological mechanisms of ligand-dependent nuclear receptor modulation. NMR spectroscopy, PPI, and cellular transcription assays show that Nurr1-RXRα transcriptional activation by RXRα ligands is not correlated with classical RXRα agonism but instead correlated with weakening Nurr1-RXRα LBD heterodimer affinity and heterodimer dissociation. Our data inform a model by which pharmacologically distinct RXRα ligands (RXRα homodimer agonists and Nurr1-RXRα heterodimer selective agonists that function as RXRα homodimer antagonists) operate as allosteric PPI inhibitors that release a transcriptionally active Nurr1 monomer from a repressive Nurr1-RXRα heterodimeric complex. These findings provide a molecular blueprint for ligand activation of Nurr1 transcription via small molecule targeting of Nurr1-RXRα.
Indexed as
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What OpenQuestion holds
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.