ArticleNature communications2023
An optimized Nurr1 agonist provides disease-modifying effects in Parkinson's disease models.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Considerations for therapeutic targets for clinical trials in biomarker-characterized prodromal Parkinson's disease populations.Journal of Parkinson's disease · 2026Article
- Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism.PLoS biology · 2026Article
- RanBP2 promotes ferroptosis resistance and compromises therapeutic response by stabilizing SLC7A1 through LRSAM1 SUMOylation and ubiquitination in lung adenocarcinoma.Cell death and differentiation · 2026Article
- Article
- Development of a Brain-Penetrant Nurr1 Agonist Tool.ChemMedChem · 2026Article
- A53T α-Synuclein Expression is Associated with Altered Dopaminergic-Like Differentiation and Reduced DNA Topoisomerase IIβ Levels in an In Vitro Model of Parkinson's Disease.Molecular neurobiology · 2026Article
- Amodiaquine Enhances Anti-Melanoma Efficacy of Attenuated Salmonella via Targeting Glutathione Reductase in Neutrophils.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nr4a2, A Key Factor Controlling the Development and Functional Maintenance of Forebrain Car3 Neurons.Neuroscience bulletin · 2026Article
- Saikosaponin A, a bioactive compound from Bupleuri radix, protects dopaminergic neurons and correlates with NURR1 expression in 6-hydroxydopamine-injected hemi-Parkinsonian mouse model.Pharmacological reports : PR · 2026Article
- The Interplay Between Nurr1 and Mitochondrial Biogenesis: Implications for Neurodegenerative Therapy.Molecular neurobiology · 2026Review
- Targeting Nurr1 With Amodiaquine Preserves Dendritic Spines and Cognitive Function After Chronic Cerebral Hypoperfusion.Neural plasticity · 2026Article
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Regulation ofInternational journal of molecular sciences · 2025Review
- Identification and Validation of Inverse Agonists for Nuclear Receptor Subfamily 4 Group A Member 2.ACS omega · 2025Article
- Integrating artificial intelligence and optogenetics for Parkinson's disease diagnosis and therapeutics in male mice.Nature communications · 2025Article
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- Article
- Subtle behavioral alterations in the spontaneous behaviors of MPTP mouse model of Parkinson's disease.Translational psychiatry · 2025Article
- Aminoquinoline-Pyrimidine-Based Alkyl-Piperazine Tethered Hybrids: Synthesis, Antiplasmodial Activity, and Mechanistic Studies.ACS omega · 2025Article
- A Nurr1 Agonist Derived from the Natural Ligand DHI Induces Neuroprotective Gene Expression.Journal of medicinal chemistry · 2025Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
The nuclear receptor, Nurr1, is critical for both the development and maintenance of midbrain dopamine neurons, representing a promising molecular target for Parkinson's disease (PD). We previously identified three Nurr1 agonists (amodiaquine, chloroquine and glafenine) that share an identical chemical scaffold, 4-amino-7-chloroquinoline (4A7C), suggesting a structure-activity relationship. Herein we report a systematic medicinal chemistry search in which over 570 4A7C-derivatives were generated and characterized. Multiple compounds enhance Nurr1's transcriptional activity, leading to identification of an optimized, brain-penetrant agonist, 4A7C-301, that exhibits robust neuroprotective effects in vitro. In addition, 4A7C-301 protects midbrain dopamine neurons in the MPTP-induced male mouse model of PD and improves both motor and non-motor olfactory deficits without dyskinesia-like behaviors. Furthermore, 4A7C-301 significantly ameliorates neuropathological abnormalities and improves motor and olfactory dysfunctions in AAV2-mediated α-synuclein-overexpressing male mouse models. These disease-modifying properties of 4A7C-301 may warrant clinical evaluation of this or analogous compounds for the treatment of patients with PD.
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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.