ArticleProceedings of the National Academy of Sciences of the United States of America2017
Nurr1:RXRα heterodimer activation as monotherapy for Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- Retinoid-X receptor action and disruption in development.Developmental biology · 2026Review
- Role of the retinoid X receptor-peroxisome proliferator-activated receptor-γ axis in adolescent attention-deficit hyperactivity disorder.European archives of psychiatry and clinical neuroscience · 2026Article
- Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.eLife · 2026Article
- The Interplay Between Nurr1 and Mitochondrial Biogenesis: Implications for Neurodegenerative Therapy.Molecular neurobiology · 2026Review
- Role of Nuclear Receptors on the Progression of Multiple Sclerosis: A Review.Cellular and molecular neurobiology · 2025Review
- Article
- BRF110, an Orally Active Nurr1-RXRα-Selective Rexinoid, Enhances BDNF Expression without Elevating Triglycerides.Journal of medicinal chemistry · 2025Article
- Vitamin A attenuates PFOS-induced neurotoxicity and alters early proximity patterns to conspecifics in zebrafish larvae.Frontiers in behavioral neuroscience · 2025Article
- RXR nuclear receptor signaling modulates lipid metabolism and triggers lysosomal clearance of alpha-synuclein in neuronal models of synucleinopathy.Cellular and molecular life sciences : CMLS · 2024Article
- Dopamine synthesis and transport: current and novel therapeutics for parkinsonisms.Biochemical Society transactions · 2024Review
- Comparative safety, pharmacokinetics, and off-target assessment of 1,1-bis(3'-indolyl)-1-(Toxicology research · 2024Article
- Retinoic Acid Prevents α-Synuclein Preformed Fibrils-Induced Toxicity via Inhibiting STAT1-PARP1 Signaling.Molecular neurobiology · 2023Article
- Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology.International journal of molecular sciences · 2023Review
- Alternative activation.eLife · 2023Article
- Article
- Systems level analysis of sex-dependent gene expression changes in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Advances in NURR1-Regulated Neuroinflammation Associated with Parkinson's Disease.International journal of molecular sciences · 2022Review
- Integrative analysis reveals structural basis for transcription activation of Nurr1 and Nurr1-RXRα heterodimer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Recruitment of the CoREST transcription repressor complexes by Nerve Growth factor IB-like receptor (Nurr1/NR4A2) mediates silencing of HIV in microglial cells.PLoS pathogens · 2022Article
- The role of NURR1 in metabolic abnormalities of Parkinson's disease.Molecular neurodegeneration · 2022Review
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the gradual depletion of dopamine (DA). Current treatments replenish the DA deficit and improve symptoms but induce dyskinesias over time, and neuroprotective therapies are nonexistent. Here we report that Nuclear receptor-related 1 (Nurr1):Retinoid X receptor α (RXRα) activation has a double therapeutic potential for PD, offering both neuroprotective and symptomatic improvement. We designed BRF110, a unique in vivo active Nurr1:RXRα-selective lead molecule, which prevents DAergic neuron demise and striatal DAergic denervation in vivo against PD-causing toxins in a Nurr1-dependent manner. BRF110 also protects against PD-related genetic mutations in patient induced pluripotent stem cell (iPSC)-derived DAergic neurons and a genetic mouse PD model. Remarkably, besides neuroprotection, BRF110 up-regulates tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC), and GTP cyclohydrolase I (GCH1) transcription; increases striatal DA in vivo; and has symptomatic efficacy in two postneurodegeneration PD models, without inducing dyskinesias on chronic daily treatment. The combined neuroprotective and symptomatic effects of BRF110 identify Nurr1:RXRα activation as a potential monotherapeutic approach for PD.
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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.