ArticleScience translational medicine2012
α-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons.
Article in Science translational medicine, 2012. 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 146 papers.
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Who cites it
146 citing papers in PubMed, 322 citations in OpenAlex.
- Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease.Brain : a journal of neurology · 2019Trial
- Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson's Disease: Rationale for Clinical Trial, and Current Progress.Journal of Parkinson's disease · 2017Trial
- Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism.PLoS biology · 2026Article
- Dysregulation of astrocytic DNAJC6 contributes to sporadic Parkinson's disease pathogenesis.The Journal of clinical investigation · 2026Article
- The Involvement of Ceramide, Sphingosine-1-Phosphate and Ganglioside GM1 in Regulating Some Nervous System Functions.International journal of molecular sciences · 2025Review
- Integrating artificial intelligence and optogenetics for Parkinson's disease diagnosis and therapeutics in male mice.Nature communications · 2025Article
- Human Pluripotent Stem Cell-Based Therapies for Parkinson's Disease: Challenges and Potential Solutions.Yonsei medical journal · 2025Review
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- Preparation of human astrocytes with potent therapeutic functions from human pluripotent stem cells using ventral midbrain patterning.Journal of advanced research · 2025Article
- A Nurr1 Agonist Derived from the Natural Ligand DHI Induces Neuroprotective Gene Expression.Journal of medicinal chemistry · 2025Article
- Gene Therapy for Parkinson's Disease Using Midbrain Developmental Genes to Regulate Dopaminergic Neuronal Maintenance.International journal of molecular sciences · 2024Review
- Neurotrophic factors for Parkinson's disease: Current status, progress, and remaining questions. Conclusions from a 2023 workshop.Journal of Parkinson's disease · 2024Review
- The Synergistic Effect Study of Lipopolysaccharide (LPS) and A53T-α-Synuclein: Intranasal LPS Exposure on the A53T-α-Synuclein Transgenic Mouse Model of Parkinson's Disease.Molecular neurobiology · 2024Article
- Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing.Communications chemistry · 2024Article
- Investigating the Effect of an Anti-Inflammatory Drug in Determining NURR1 Expression and Thus Exploring the Progression of Parkinson's Disease.Physiological research · 2024Article
- Some Novel Therapies in Parkinson's Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature.Biomedicines · 2024Review
- Adeno-associated virus (AAV) 9-mediated gene delivery of Nurr1 and Foxa2 ameliorates symptoms and pathologies of Alzheimer disease model mice by suppressing neuro-inflammation and glial pathology.Molecular psychiatry · 2023Article
- Structure-Guided Design of Nurr1 Agonists Derived from the Natural Ligand Dihydroxyindole.Journal of medicinal chemistry · 2023Article
- The relationship between depletion of brain GM1 ganglioside and Parkinson's disease.FEBS open bio · 2023Review
- Single-nuclei RNA sequencing uncovers heterogenous transcriptional signatures in Parkinson's disease associated with nuclear receptor-related factor 1 defect.Neural regeneration research · 2023Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glial cell line-derived neurotrophic factor (GDNF) and its close relative neurturin are currently in clinical trials for neuroprotection in patients with Parkinson disease (PD). However, in animal models of PD, GDNF fails to protect nigral dopamine (DA) neurons against α-synuclein-induced neurodegeneration. Using viral vector delivery of human wild-type α-synuclein to nigral DA neurons in rats, we show that the intracellular response to GDNF is blocked in DA neurons that overexpress α-synuclein. This block is accompanied by reduced expression of the transcription factor Nurr1 and its downstream target, the GDNF receptor Ret. We found that Ret expression was also reduced in nigral DA neurons in PD patients. Conditional knockout of Nurr1 in mice resulted in reduced Ret expression and blockade of the response to GDNF, whereas overexpression of Nurr1 restored signaling, providing protection of nigral DA neurons against α-synuclein toxicity. These results suggest that Nurr1 is a regulator of neurotrophic factor signaling and a key player in the cellular defense against α-synuclein toxicity.
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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.