ArticleFrontiers in aging neuroscience2021
Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson's Disease. A Systematic Review.
Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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.
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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- BDNF and GDNF in Parkinson's Disease: Associations with Clinical Features, Disease Course, and Progression-A Systematic Review.Molecular neurobiology · 2026Pooled it
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Application of neurodegenerative disease treatment strategies in tinnitus: mechanisms, translation, and prospects.Frontiers in aging neuroscience · 2026Review
- Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A ComprehensiveCurrent medicinal chemistry · 2025Article
- Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.Gene therapy · 2024Article
- Level of glial cell derived neurotrophic factor in the blood plasma of rheumatoid arthritis patients and its relationship with alexithymia.Reumatologia · 2024Article
- Single-nuclei RNA sequencing uncovers heterogenous transcriptional signatures in Parkinson's disease associated with nuclear receptor-related factor 1 defect.Neural regeneration research · 2023Article
- Functional Impairment of the Nervous System with Glycolipid Deficiencies.Advances in neurobiology · 2023Article
- Striatonigral distribution of a fluorescent reporter following intracerebral delivery of genome editors.Frontiers in bioengineering and biotechnology · 2023Article
- Bimodal regulation of axonal transport by the GDNF-RET signalling axis in healthy and diseased motor neurons.Cell death & disease · 2022Article
- Progress, Opportunities, and Challenges of Magneto-Plasmonic Nanoparticles under Remote Magnetic and Light Stimulation for Brain-Tissue and Cellular Regeneration.Nanomaterials (Basel, Switzerland) · 2022Review
- Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation.International journal of molecular sciences · 2022Article
- Therapeutic Strategies for Immune Transformation in Parkinson's Disease.Journal of Parkinson's disease · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative maladies with unforeseen complex pathologies. While this neurodegenerative disorder's neuropathology is reasonably well known, its etiology remains a mystery, making it challenging to aim therapy. Glial cell-line derived neurotrophic factor (GDNF) remains an auspicious therapeutic molecule for treating PD. Neurotrophic factor derived from glial cell lines is effective in rodents and nonhuman primates, but clinical findings have been equivocal. Laborious exertions have been made over the past few decades to improve and assess GDNF in treating PD (clinical studies). Definitive clinical trials have, however, failed to demonstrate a survival advantage. Consequently, there seemed to be a doubt as to whether GDNF has merit in the potential treatment of PD. The purpose of this cutting edge review is to speculate as to why the clinical trials have failed to meet the primary endpoint. We introduce a hypothesis, "Failure of GDNF in clinical trials succumbed by nuclear receptor-related factor 1 (Nurr1) shortfall." We demonstrate how Nurr1 binds to GDNF to induce dopaminergic neuron synthesis. Due to its undisputable neuro-protection aptitude, we display Nurr1 (also called Nr4a2) as a promising therapeutic target for 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.