ArticleMolecular neurodegeneration2012
Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes.HGG advances · 2024Pooled it
- Direct neuronal reprogramming: emerging therapeutic strategies for neurodegenerative disorders.Annals of medicine · 2026Review
- DNA Topoisomerase IIβ Suppresses Microglial Inflammatory Cytokine Release: A Potential Regulator of Neuroinflammation.Neurochemical research · 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
- Early α-Synuclein Pathology Induces Neuroinflammation and Decreases Topoisomerase IIβ Expression in A53T Mice.Inflammation · 2025Article
- Molecular Determinants of A9 Dopaminergic Neurons.Neuromolecular medicine · 2025Review
- Top2b regulates morphological and migratory properties of retinal progenitor cells in vivo and upon transplantable matrix substrates.Exploration of biomat-x · 2025Article
- Single-cell RNA sequencing of aging neural progenitors reveals loss of excitatory neuron potential and a population with transcriptional immune response.Frontiers in neuroscience · 2024Article
- The role of Nurr1-miR-30e-5p-NLRP3 axis in inflammation-mediated neurodegeneration: insights from mouse models and patients' studies in Parkinson's disease.Journal of neuroinflammation · 2023Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.International journal of molecular sciences · 2022Article
- TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.Molecular neurobiology · 2022Article
- The role of NURR1 in metabolic abnormalities of Parkinson's disease.Molecular neurodegeneration · 2022Review
- Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons.International journal of molecular sciences · 2022Review
- Recent Progress in Non-motor Features of Parkinson's Disease with a Focus on Circadian Rhythm Dysregulation.Neuroscience bulletin · 2021Review
- Assessment of NR4A Ligands That Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1.Journal of medicinal chemistry · 2020Article
- Molecular Mechanisms Involved in Neural Substructure Development during Phosphodiesterase Inhibitor Treatment of Mesenchymal Stem Cells.International journal of molecular sciences · 2020Article
- Intrastriatal alpha-synuclein fibrils in monkeys: spreading, imaging and neuropathological changes.Brain : a journal of neurology · 2019Article
- Molecular Insights into NR4A2(Nurr1): an Emerging Target for Neuroprotective Therapy Against Neuroinflammation and Neuronal Cell Death.Molecular neurobiology · 2019Review
- TOP2B: The First Thirty Years.International journal of molecular sciences · 2018Review
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNURR1 (also named as NR4A2) is a member of the steroid/thyroid hormone receptor family, which can bind to DNA and modulate expression of target genes. Previous studies have shown that NURR1 is essential for the nigral dopaminergic neuron phenotype and function maintenance, and the defects of the gene are possibly associated with Parkinson's disease (PD).
resultsIn this study, we used new born Nurr1 knock-out mice combined with Affymetrix genechip technology and real time polymerase chain reaction (PCR) to identify Nurr1 regulated genes, which led to the discovery of several transcripts differentially expressed in the nigro-striatal pathway of Nurr1 knock-out mice. We found that an axon genesis gene called Topoisomerase IIβ (Top IIβ) was down-regulated in Nurr1 knock-out mice and we identified two functional NURR1 binding sites in the proximal Top IIβ promoter. While in Top IIβ null mice, we saw a significant loss of dopaminergic neurons in the substantial nigra and lack of neurites along the nigro-striatal pathway. Using specific TOP II antagonist ICRF-193 or Top IIβ siRNA in the primary cultures of ventral mesencephalic (VM) neurons, we documented that suppression of TOP IIβ expression resulted in VM neurites shortening and growth cones collapsing. Furthermore, microinjection of ICRF-193 into the mouse medial forebrain bundle (MFB) led to the loss of nigro-striatal projection.
conclusionTaken together, our findings suggest that Top IIβ might be a down-stream target of Nurr1, which might influence the processes of axon genesis in dopaminergic neurons via the regulation of TOP IIβ expression. The Nurr1-Top IIβ interaction may shed light on the pathologic role of Nurr1 defect in the nigro-striatal pathway deficiency associated with PD.
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