research feed

Every NR4A2 paper, in plain English

PubMed and the Europe PMC preprint servers are queried daily for NR4A2 and NURR1, back to the earliest records. Each abstract is summarised locally by Qwen3.6 35B and tagged by relevance to a parent of an NR4A2 child. Source links go straight to the paper.

subscribe (Atom feed) · high and medium relevance only

registered clinical trials

Every ClinicalTrials.gov study whose record mentions NR4A2 or NURR1. Most use NURR1 as a Parkinson's biomarker rather than testing anything for this syndrome, so read the conditions line. Studies still open come first. Last checked 2026-09-14.

completed or inactive (4) ›
medium2006-02-13 · Proceedings of the National Academy of Sciences of the United States of America

Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype.

Martinat C, Bacci JJ, Leete T, Kim J, Vanti WB, Newman AH, Cha JH, Gether U, Wang H, Abeliovich A

Nurr1 and Pitx3 work together to mature stem cells into midbrain dopamine neurons in laboratory cultures. This finding identifies a specific molecular partnership required for the development of these critical brain cells.

  • Nurr1 and Pitx3 cooperate to drive stem cell maturation into dopamine neurons.
  • Neither factor alone is sufficient to induce the mature neuron phenotype.
  • This mechanism was observed in both mouse and human embryonic stem cells.
  • The study focuses on basic developmental biology rather than clinical treatment.
medium2006-02-01 · Development (Cambridge, England)

Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons.

Kele J, Simplicio N, Ferri AL, Mira H, Guillemot F, Arenas E, Ang SL

Neurogenin 2 drives the formation of midbrain dopaminergic neurons, which are the same cell type affected in NR4A2-related syndromes. This study shows that Neurogenin 2 is essential for these neurons to develop from stem cells into mature, functional nerve cells.

  • Neurogenin 2 is required for midbrain dopaminergic neuron development.
  • It helps progenitor cells become Nurr1-positive precursors.
  • Nurr1 is the protein encoded by the NR4A2 gene.
  • Mash1 can partially compensate if Neurogenin 2 is missing.
  • This confirms a specific genetic pathway for these neurons.
medium2005-09-01 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice.

Imam SZ, Jankovic J, Ali SF, Skinner JT, Xie W, Conneely OM, Le WD

Mice with one copy of the Nurr1 gene show higher levels of nitric oxide, which triggers cell death pathways in dopamine neurons. This mechanism explains why these mice are more sensitive to damage from dopaminergic toxins like methamphetamine.

  • Nurr1 heterozygous mice have elevated neuronal nitric oxide synthase in the striatum.
  • Increased nitric oxide activates apoptotic cascades via cytochrome C and caspase-3.
  • Methamphetamine exposure worsens these cellular damage markers in Nurr1 +/- mice.
  • The study identifies a specific molecular pathway for dopamine neuron vulnerability.
medium2005-09-01 · Movement disorders : official journal of the Movement Disorder Society

Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study.

Karamohamed S, Golbe LI, Mark MH, Lazzarini AM, Suchowersky O, Labelle N, Guttman M, Currie LJ, Wooten GF, Stacy M, Saint-Hilaire M, Feldman RG, Liu J, Shoemaker CM, Wilk JB, DeStefano AL, Latourelle JC, Xu G, Watts R, Growdon J, Lew M, Waters C, Vieregge P, Pramstaller PP, Klein C, Racette BA, Perlmutter JS, Parsian A, Singer C, Montgomery E, Baker K, Gusella JF, Herbert A, Myers RH

This study screened for specific NR4A2 variants in families with Parkinson's disease and found none of the previously reported mutations. The results indicate that these particular variants do not contribute to familial Parkinson's disease in this cohort.

  • Researchers tested 292 familial Parkinson's disease cases from the GenePD study.
  • Six specific genetic variations in SCNA, NR4A2, and DJ-1 were analyzed.
  • None of the targeted NR4A2 variants were found in any participant.
  • Other genes or variants likely account for the familial risk in these families.
medium2005-07-11 · Mutation research

In search of genes involved in neurodegenerative disorders.

Pardo LM, van Duijn CM

This review identifies NR4A2 as one of the seven genes linked to Parkinson's disease, noting that these genetic findings mostly explain early-onset cases rather than the common forms of the disorder. The paper summarizes current knowledge on Alzheimer's and Parkinson's genetics but does not provide new clinical data or treatment insights for NR4A2-related syndromes.

  • NR4A2 is one of seven genes associated with Parkinson's disease.
  • These identified genes primarily explain early-onset cases of the disorder.
  • The paper reviews genetics of Alzheimer's and Parkinson's broadly.
  • It discusses hypotheses about common versus rare genetic variants.
  • No specific clinical data or treatment options for NR4A2 are presented.
lower-relevance papers (35) ›
low2006-03-01 · Journal of neuroscience research

Influence of retinoic acid and lithium on proliferation and dopaminergic potential of human NT2 cells.

Misiuta IE, Saporta S, Sanberg PR, Zigova T, Willing AE

Lithium increases the survival and growth of human neural precursor cells in a dish but does not boost the expression of key genes needed for dopamine neuron development. Retinoic acid-treated neurons lose specific developmental markers, while lithium fails to restore or increase critical transcription factors like Nurr1.

  • Lithium boosts viability and proliferation of human neural precursor cells in culture.
  • Lithium does not increase expression of Nurr1 or other dopamine-related transcription factors.
  • Retinoic acid-treated neurons lose Engrailed-1 and Ptx3 expression markers.
  • The study uses an in vitro cell line model, not human patients or animals.
low2006-03-01 · Experimental dermatology

The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory disease.

O'Kane M, Murphy EP, Kirby B

This study explores how stress hormones influence skin inflammation and mentions that the hormone CRH can trigger the production of NURR1, a protein related to NR4A2. It does not provide any clinical data, treatment insights, or direct evidence relevant to NR4A2-related neurodevelopmental syndromes.

  • The paper focuses on skin inflammation and stress responses, not neurological development.
  • It identifies NURR1 as a downstream effect of CRH in inflammatory skin conditions.
  • No human clinical data or NR4A2 variant analysis is presented.
  • The link between NURR1 and psoriasis treatment is noted but not explored for NR4A2.
low2006-02-10 · Experimental neurology

Identification of novel genes regulated in the developing human ventral mesencephalon.

Jørgensen JR, Juliusson B, Henriksen KF, Hansen C, Knudsen S, Petersen TN, Blom N, Seiger A, Wahlberg LU

This study maps gene activity in the developing human brain to identify factors that guide dopamine neuron formation, providing a foundational map for future regenerative therapies. It confirms known dopamine markers and highlights several new genes with potential roles in this developmental process.

  • Researchers compared gene expression in ventral versus dorsal regions of the human embryonic midbrain.
  • The analysis validated known dopamine neuron markers like NURR1, TH, and FOXA1.
  • Fifteen new transcripts showed distinct temporal and regional expression patterns during development.
  • Findings aim to inform cell replacement strategies for Parkinson's disease rather than NR4A2 syndrome treatment.
low2006-02-10 · American journal of respiratory cell and molecular biology

Gene induction during differentiation of human pulmonary type II cells in vitro.

Wade KC, Guttentag SH, Gonzales LW, Maschhoff KL, Gonzales J, Kolla V, Singhal S, Ballard PL

This study profiles gene expression changes in human lung cells as they mature, identifying NR4A2 as one of many genes upregulated during this process. It does not investigate the brain, dopamine pathways, or any potential treatments for NR4A2-related syndromes.

  • Researchers studied human fetal lung cells maturing into type II cells in a lab dish.
  • NR4A2 gene expression increased significantly during this specific lung cell differentiation process.
  • The study focuses on pulmonary surfactant production, not neurological function.
  • No clinical data or treatment implications for NR4A2 syndromes are presented.
low2006-02-08 · Nuclear receptor signaling

The NR4A subgroup: immediate early response genes with pleiotropic physiological roles.

Maxwell MA, Muscat GE

This review describes the general molecular structure and signaling mechanisms of the NR4A gene family, including Nurr1 (NR4A2). It explains how these proteins function as ligand-independent transcription factors that respond to various cellular stimuli. The paper does not provide specific clinical data or treatment insights for NR4A2-related syndromes.

  • NR4A genes include Nur77, Nurr1, and NOR-1, which act as immediate early response genes.
  • These receptors activate gene expression without needing a traditional ligand binding.
  • Nurr1 is implicated in neurological disease among other physiological processes.
  • The study focuses on molecular biology rather than human clinical outcomes.
low2006-02-01 · The Biochemical journal

Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation.

Wingate AD, Campbell DG, Peggie M, Arthur JS

This study identifies the specific enzymes that modify the NR4A2 protein (Nur77) in response to cell growth signals. It confirms that RSK phosphorylates NR4A2 and two related proteins, Nurr1 and Nor1, at a site previously linked to DNA binding changes. The findings describe basic molecular mechanisms without offering clinical insights or treatment options for NR4A2-related syndromes.

  • RSK phosphorylates Nur77 (NR4A2) in cells following mitogenic stimulation.
  • Nurr1 and Nor1 receive identical phosphorylation from RSK at equivalent sites.
  • Phosphorylation promotes binding to 14-3-3 proteins in vitro but not in cells.
  • The study focuses on molecular mechanics with no clinical application.
low2006-01-24 · Experimental neurology

Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon.

Thompson LH, Andersson E, Jensen JB, Barraud P, Guillemot F, Parmar M, Björklund A

Researchers identify a specific precursor cell type in the developing brain that can generate dopamine neurons and survive transplantation. This finding provides a method to isolate these cells for potential future neural repair strategies.

  • Neurogenin2 marks only dopamine neuron precursors, not other neuron types or glia.
  • Isolated precursor cells mature into dopamine neurons after transplantation in rat models.
  • The study uses mouse genetics and rat transplants, not human subjects.
  • No direct treatment for NR4A2 syndrome is tested or proposed here.
low2006-01-20 · The Journal of comparative neurology

Nurr1 in Parkinson's disease and related disorders.

Chu Y, Le W, Kompoliti K, Jankovic J, Mufson EJ, Kordower JH

This study shows that Nurr1 protein levels drop in specific brain neurons when they contain pathological clumps associated with Parkinson's, Alzheimer's, and PSP. The reduction of Nurr1 correlates with the loss of dopamine-producing markers, suggesting it is a consequence of neurodegeneration rather than a primary cause.

  • Nurr1 levels decrease in substantia nigra neurons containing alpha-synuclein clumps in Parkinson's disease.
  • Nurr1 levels also drop in Alzheimer's cases with neurofibrillary tangles and severely in PSP cases.
  • The decline in Nurr1 matches the loss of tyrosine hydroxylase, a key dopamine enzyme marker.
  • This finding links Nurr1 deficiency to intracellular pathology across multiple neurodegenerative diseases.
low2006-01-01 · Sheng li ke xue jin zhan [Progress in physiology]

[Recent advances in Nurr1 gene differentiating stem cells into dopaminergic neuron].

Gao FY, Yang H, Zhang ZY

This review summarizes how stem cells are converted into dopamine-producing neurons using the Nurr1 gene. It outlines current laboratory techniques for generating these specific nerve cells from undifferentiated sources.

  • The paper reviews methods for differentiating stem cells into dopaminergic neurons.
  • It focuses on the role of the Nurr1 gene in this cellular transformation process.
  • The content is limited to basic laboratory techniques and molecular mechanisms.
  • No human clinical data or patient outcomes are presented in this review.
low2006-01-01 · Cell transplantation

One-step induction of neurons from mouse embryonic stem cells in serum-free media containing vitamin B12 and heparin.

Yamazoe H, Kobori M, Murakami Y, Yano K, Satoh M, Mizuseki K, Sasai Y, Iwata H

Researchers developed a simplified method to convert mouse embryonic stem cells into dopamine-releasing neurons using vitamin B12 and heparin. This technique produces midbrain dopaminergic neurons that express Nurr1 and release dopamine, offering a potential cell source for Parkinson's disease transplantation therapies.

  • Mouse stem cells differentiate into dopamine-releasing neurons without expensive cytokines.
  • Vitamin B12 and heparin drive the formation of midbrain dopaminergic cells expressing Nurr1.
  • The method aims to provide cells for Parkinson's disease transplantation therapies.
  • Additional supplements increase neuron yield but are not strictly required for induction.
low2006-01-01 · Journal of neural transmission. Supplementum

The role of Pitx3 in survival of midbrain dopaminergic neurons.

Smits SM, Smidt MP

This review explains how the transcription factor Pitx3 directs the development and survival of midbrain dopaminergic neurons. It highlights that understanding these genetic pathways is essential for future therapies, such as stem cell treatments for Parkinson's disease.

  • Pitx3 regulates the specification and differentiation of midbrain dopaminergic neurons.
  • The paper reviews molecular mechanisms rather than clinical outcomes or treatments.
  • Findings support potential stem cell strategies for Parkinson's disease therapy.
low2006-01-01 · Learning & memory (Cold Spring Harbor, N.Y.)

Knockdown of Nurr1 in the rat hippocampus: implications to spatial discrimination learning and memory.

Colón-Cesario WI, Martínez-Montemayor MM, Morales S, Félix J, Cruz J, Adorno M, Pereira L, Colón N, Maldonado-Vlaar CS, Peña de Ortiz S

Reducing Nurr1 levels in the rat hippocampus impairs spatial learning and memory consolidation. The study shows that lower Nurr1 causes difficulties in adapting to new spatial rules, suggesting a role in cognitive flexibility.

  • Lower Nurr1 in rat hippocampus impairs spatial discrimination learning.
  • Pre-training reduction harms long-term memory formation.
  • Post-training reduction disrupts acquiring new task rules.
  • Animals show perseveration, struggling to unlearn old patterns.
low2005-12-08 · Molecular endocrinology (Baltimore, Md.)

Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77.

Pei L, Castrillo A, Tontonoz P

This study shows that NR4A2 and related proteins promote inflammation in immune cells rather than protecting them. It identifies a specific mechanism where these proteins activate genes that amplify inflammatory signals, which is unrelated to the neurodevelopmental or dopaminergic functions relevant to your child's condition.

  • NR4A2 acts as a pro-inflammatory factor in macrophages.
  • It activates genes involved in inflammation and cell cycle control.
  • The study focuses on immune system biology, not brain development.
  • No findings relate to NR4A2-related syndrome phenotypes or treatments.
low2005-12-01 · Differentiation; research in biological diversity

Human fibroblast-derived cell lines have characteristics of embryonic stem cells and cells of neuro-ectodermal origin.

Rieske P, Krynska B, Azizi SA

This study shows that human fibroblast cell lines can express markers of embryonic stem cells and neuroectodermal neurons, including the NR4A2-related transcription factor Nurr-1. The cells demonstrate the ability to differentiate into neuron-like cells under specific culture conditions.

  • Fibroblast-derived MRC-5 cells express pluripotency and neuroectodermal markers.
  • The cells naturally express Nurr-1, a key transcription factor in NR4A2 biology.
  • Researchers induced these cells to produce tyrosine hydroxylase, a neuronal enzyme.
  • This is an in vitro cell line study with no human clinical data.
low2005-12-01 · Journal of neurochemistry

Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity.

Michelhaugh SK, Vaitkevicius H, Wang J, Bouhamdan M, Krieg AR, Walker JL, Mendiratta V, Bannon MJ

Dopamine neurons naturally produce several truncated versions of the NR4A2 protein that have significantly reduced or no ability to activate genes. These inactive variants act as dominant negatives, potentially interfering with the function of the full-length NR4A2 protein. This natural variation suggests a complex regulatory mechanism for dopamine neuron development and maintenance.

  • NR4A2 exists in multiple splice variants in human and rat dopamine neurons.
  • Truncated variants show significantly reduced transcriptional activity compared to full-length NR4A2.
  • Some inactive variants act as dominant negatives, potentially blocking normal NR4A2 function.
  • These variants constitute 20-35% of NR4A2 transcripts in the rat midbrain.
low2005-12-01 · The Journal of investigative dermatology

Differential expression of genes involved in skin homing, proliferation, and apoptosis in CD4+ T cells of patients with atopic dermatitis.

Hijnen D, Nijhuis E, Bruin-Weller M, Holstege F, Koerkamp MG, Kok I, Bruijnzeel-Koomen C, Knol E

CD4+ T cells in people with atopic dermatitis show altered gene activity related to moving to skin, cell growth, and cell death, even without stimulation. These changes occur without major shifts in classic allergy-related genes.

  • AD patients have abnormal CD4+ T cell gene activity
  • Genes linked to skin targeting and cell growth are altered
  • No major changes in typical Th1/Th2 allergy genes
  • Findings suggest immune cells are primed in AD
  • Changes seen in unstimulated blood cells
low2005-11-25 · Journal of inflammation (London, England)

Nurr1 dependent regulation of pro-inflammatory mediators in immortalised synovial fibroblasts.

Davies MR, Harding CJ, Raines S, Tolley K, Parker AE, Downey-Jones M, Needham MR

This study finds that Nurr1 promotes inflammation in joint cells by increasing the production of specific signaling proteins. The research uses a cell line model to show these effects, which are unrelated to the neurological development or dopamine pathways relevant to NR4A2 syndrome.

  • Nurr1 increases pro-inflammatory gene expression in synovial fibroblasts.
  • The study focuses on rheumatoid arthritis pathogenesis, not neurodevelopment.
  • Results come from immortalized cell lines, not human patients or animal models of NR4A2.
  • No findings relate to dopaminergic neurons, movement disorders, or cognitive outcomes.
low2005-11-10 · Biochemical pharmacology

Selective allosteric ligand activation of the retinoid X receptor heterodimers of NGFI-B and Nurr1.

Morita K, Kawana K, Sodeyama M, Shimomura I, Kagechika H, Makishima M

Researchers identify a specific compound, HX600, that selectively activates the NR4A2 (Nurr1) and NGFI-B receptors by binding to their partner RXR receptor. This finding provides a molecular tool for studying how these receptors function in neurons. The study does not test treatments in humans or animal models of disease.

  • HX600 selectively activates NR4A2 and NGFI-B heterodimers via the RXR partner.
  • The compound acts through an allosteric mechanism distinct from natural ligands.
  • This work serves as a research tool for studying receptor function.
  • No clinical data or disease model results are reported.
low2005-10-21 · Progress in neurobiology

The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease.

Jankovic J, Chen S, Le WD

This review summarizes how the Nurr1 protein guides the development and survival of dopamine-producing neurons and regulates key enzymes for dopamine production. It highlights that reduced Nurr1 levels are found in Parkinson's disease brains and blood cells, linking the gene to neurodegeneration.

  • Nurr1 controls genes essential for making and storing dopamine in brain neurons.
  • Mice lacking Nurr1 show impaired dopamine function and neuron vulnerability.
  • Parkinson's patients have lower Nurr1 levels in brain tissue and blood cells.
  • Several gene variants are associated with Parkinson's disease risk.
low2005-10-21 · Molecular and cellular neurosciences

Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion.

Castelo-Branco G, Sousa KM, Bryja V, Pinto L, Wagner J, Arenas E

Ventral midbrain glial cells secrete Wnt-5a to help neural precursors develop into dopamine-producing neurons. This process relies on region-specific transcription factors and is partially blocked when Wnt-5a signaling is inhibited.

  • Midbrain glia, not cortical glia, produce high levels of Wnt-5a.
  • Wnt-5a helps Nurr1 precursors become tyrosine hydroxylase-positive neurons.
  • Blocking Wnt-5a reduces the induction of dopaminergic neurons.
  • This mechanism explains how glia support dopamine neuron development.
low2005-10-01 · Stem cells and development

NTera2: a model system to study dopaminergic differentiation of human embryonic stem cells.

Schwartz CM, Spivak CE, Baker SC, McDaniel TK, Loring JF, Nguyen C, Chrest FJ, Wersto R, Arenas E, Zeng X, Freed WJ, Rao MS

This study demonstrates that the NTera2 cell line can differentiate into functional dopaminergic neurons when exposed to specific conditioning media. The research validates this cell model as a surrogate for human embryonic stem cells in studying neuronal development.

  • NTera2 cells express key dopaminergic markers like Nurr1 and tyrosine hydroxylase after differentiation.
  • Conditioned media from PA6 cells drives the maturation of NTera2 into functional neurons.
  • The system provides a model for studying human embryonic stem cell differentiation pathways.
low2005-09-15 · The Biochemical journal

MSKs are required for the transcription of the nuclear orphan receptors Nur77, Nurr1 and Nor1 downstream of MAPK signalling.

Darragh J, Soloaga A, Beardmore VA, Wingate AD, Wiggin GR, Peggie M, Arthur JS

This study identifies the molecular mechanism by which cellular stress signals activate the NR4A2 gene (Nurr1) through specific kinase pathways in mouse cells. It confirms that MSK kinases and CREB are essential for Nurr1 transcription but does not test any treatments or involve human patients.

  • MSK kinases drive Nurr1 transcription via CREB phosphorylation in mouse fibroblasts.
  • Stress signals like TNF activate this pathway, while growth factors use partial pathways.
  • A second ERK pathway activates Nurr1 independently of MSK and CREB.
  • The research focuses on basic gene regulation mechanisms in non-neuronal cells.
low2005-09-01 · Biological & pharmaceutical bulletin

Prostaglandin A2 acts as a transactivator for NOR1 (NR4A3) within the nuclear receptor superfamily.

Kagaya S, Ohkura N, Tsukada T, Miyagawa M, Sugita Y, Tsujimoto G, Matsumoto K, Saito H, Hashida R

Prostaglandin A2 directly activates the NOR1 protein, which is a different member of the same nuclear receptor family as NR4A2. This study identifies a potential mechanism for modulating NOR1 activity using specific compounds.

  • Prostaglandin A2 binds to and activates the NOR1 transcription factor.
  • NOR1 is part of the NR4A subfamily, distinct from NR4A2 (Nurr1).
  • The study uses mouse spleen cells and reporter systems.
  • No human data or clinical trials are reported.
  • Findings do not directly address NR4A2-related syndrome mechanisms.
low2005-08-25 · Stem cells (Dayton, Ohio)

Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells.

Kim DW, Chung S, Hwang M, Ferree A, Tsai HC, Park JJ, Chung S, Nam TS, Kang UJ, Isacson O, Kim KS

This study demonstrates that combining genetic modification with specific growth factors efficiently produces functional dopamine-producing neurons from mouse stem cells. While the method shows promise for cell replacement therapies in Parkinson's disease, it relies entirely on preclinical animal models and does not address human NR4A2-related syndromes.

  • Mouse embryonic stem cells generate high yields of functional dopamine neurons using Nurr1 and specific signals.
  • The approach improves neuron integration after transplantation into mouse brains.
  • Results suggest potential for cell therapy in Parkinson's disease, not NR4A2 syndrome.
  • No human data or clinical trials are included in this research.
low2005-08-22 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Electromagnetic fields affect transcript levels of apoptosis-related genes in embryonic stem cell-derived neural progenitor cells.

Nikolova T, Czyz J, Rolletschek A, Blyszczuk P, Fuchs J, Jovtchev G, Schuderer J, Kuster N, Wobus AM

Exposure to electromagnetic fields affects gene activity related to cell death and growth in early neural cells, but does not cause lasting harm or changes in cell function. These changes are temporary and likely compensated for by the cells' natural processes.

  • EMF exposure alters apoptosis and cell cycle genes in neural progenitor cells
  • No lasting effects on cell survival, DNA integrity, or function were found
  • Changes in gene activity were temporary and not linked to cell damage
  • Nurr1 gene was down-regulated by radiofrequency EMF
  • Cells showed no significant changes in proliferation or mitochondrial function
low2005-08-19 · Biochemical and biophysical research communications

Thiazolidinediones inhibit TNFalpha induction of PAI-1 independent of PPARgamma activation.

Liu HB, Hu YS, Medcalf RL, Simpson RW, Dear AE

This study shows that certain diabetes drugs block inflammatory signals in blood vessel cells by affecting the Nur77/Nurr1 proteins, but it does not test these effects in the brain or on motor symptoms. The findings are limited to cell culture models of vascular biology and do not provide evidence for treating NR4A2-related neurological conditions.

  • The study uses endothelial cell lines, not brain tissue or animal models relevant to NR4A2 syndrome.
  • It investigates vascular inflammation and PAI-1 levels, unrelated to dopaminergic neuron function.
  • No clinical data, human genetics, or neurological outcomes are reported.
  • The mechanism involves PPARgamma-independent pathways in blood vessels, not central nervous system repair.
low2005-08-01 · Parkinsonism & related disorders

Neurochemical characterization of dopaminergic neurons in human striatum.

Cossette M, Lévesque D, Parent A

This study maps the chemical identity of dopamine-producing neurons that naturally exist within the human striatum, finding they are mature interneurons that release both dopamine and GABA. It does not investigate NR4A2 mutations, disease mechanisms, or potential treatments for NR4A2-related syndromes.

  • Identifies a distinct population of mature dopamine-GABA co-releasing interneurons in the human striatum.
  • Confirms these neurons express Nurr1, DAT, and NeuN markers.
  • Provides baseline neuroanatomy data with no direct link to NR4A2 pathology or therapy.
low2005-07-01 · Biochemical and biophysical research communications

Parathyroid hormone induces the NR4A family of nuclear orphan receptors in vivo.

Pirih FQ, Aghaloo TL, Bezouglaia O, Nervina JM, Tetradis S

Parathyroid hormone rapidly increases NR4A gene expression in bone and kidney tissues through a specific signaling pathway. This study confirms that these genes respond to hormonal signals in living animals, mirroring earlier cell culture findings. The research focuses on skeletal biology rather than neurological development or function.

  • Parathyroid hormone triggers NR4A gene expression in bones and kidneys within one hour.
  • The effect occurs via the cAMP-PKA signaling pathway in living animals.
  • Nur77 shows the highest expression levels among the three NR4A family members.
  • The study investigates bone metabolism mechanisms, not brain or nerve function.
low2005-07-01 · Journal of immunology (Baltimore, Md. : 1950)

Modulation of orphan nuclear receptor NURR1 expression by methotrexate in human inflammatory joint disease involves adenosine A2A receptor-mediated responses.

Ralph JA, McEvoy AN, Kane D, Bresnihan B, FitzGerald O, Murphy EP

Methotrexate reduces NURR1 levels in the joints of patients with psoriatic arthritis, and this reduction correlates with improved disease activity. The drug achieves this effect by triggering adenosine release, which activates specific receptors to suppress NURR1 expression in joint tissues.

  • Methotrexate lowers NURR1 levels in the synovial tissue of psoriatic arthritis patients.
  • Reduced NURR1 correlates with decreased clinical disease activity scores.
  • The effect is mediated by adenosine acting on A2A receptors.
  • This study focuses on inflammatory joint disease, not NR4A2-related neurological syndromes.
low2005-06-28 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise.

Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA

This study maps how gene activity changes in human skeletal muscle after intense exercise, identifying shifts in metabolism, stress response, and electrolyte transport. It confirms that NR4A2 family genes (Nur77, Nurr1, Nor1) are part of the normal transcriptional response to physical exertion but does not investigate their role in neurological development or disease.

  • Researchers measured mRNA changes in human muscle before and after endurance cycling.
  • Exercise triggers significant increases in genes related to metabolism and stress response.
  • NR4A2 family members (Nur77, Nurr1, Nor1) are activated during exercise recovery.
  • The study focuses on muscle adaptation, not brain development or NR4A2 syndromes.
low2005-06-17 · The Journal of biological chemistry

Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli.

Pei L, Castrillo A, Chen M, Hoffmann A, Tontonoz P

NR4A2 (Nurr1) is rapidly turned on in immune cells called macrophages when the body is fighting inflammation, and this activation is driven by the NF-kappaB pathway, which is also involved in many inflammatory diseases.

  • NR4A2 is strongly induced by inflammation in macrophages
  • The NF-kappaB pathway controls NR4A2 activation
  • NR4A2 appears in human atherosclerotic plaques
  • This suggests NR4A2 may influence inflammatory diseases
low2005-06-02 · International archives of allergy and immunology

NR4A orphan nuclear receptor family in peripheral blood eosinophils from patients with atopic dermatitis and apoptotic eosinophils in vitro.

Kagaya S, Hashida R, Ohkura N, Tsukada T, Sugita Y, Terakawa M, Tsujimoto G, Katsunuma T, Akasawa A, Matsumoto K, Saito H

This study finds that NR4A family genes are elevated in the immune cells of patients with atopic dermatitis and regulates cell death pathways in those cells. It does not provide information on NR4A2-related neurodevelopmental syndromes, brain function, or potential treatments for children with this condition.

  • NR4A genes are higher in blood immune cells of atopic dermatitis patients.
  • The study focuses on eosinophil apoptosis, not neurological development.
  • No findings relate to NR4A2 mutations or pediatric neurodevelopmental disorders.
  • Results describe immune system mechanisms unrelated to the child's condition.
low2005-06-01 · Journal of neurochemistry

Transcriptional regulation of tyrosine hydroxylase by estrogen: opposite effects with estrogen receptors alpha and beta and interactions with cyclic AMP.

Maharjan S, Serova L, Sabban EL

Estrogen regulates the tyrosine hydroxylase gene through complex interactions with other signaling pathways, specifically involving overlapping DNA binding sites for estrogen receptors and cyclic AMP response elements. This study identifies specific molecular mechanisms by which estradiol influences TH transcription in neuronal cells depending on the estrogen receptor subtype present.

  • Estrogen increases tyrosine hydroxylase expression via ERalpha but decreases it via ERbeta.
  • The effect requires an overlapping DNA site shared with cyclic AMP response elements.
  • Estradiol reduces the transcriptional boost normally caused by cyclic AMP analogs.
  • This work uses PC12 cell lines and does not involve human patients or animal models.
low2005-06-01 · Journal of molecular endocrinology

TRAP220 is modulated by the antineoplastic agent 6-Mercaptopurine, and mediates the activation of the NR4A subgroup of nuclear receptors.

Wansa KD, Muscat GE

The cancer drug 6-Mercaptopurine activates NR4A nuclear receptors by modifying the activity of a helper protein called TRAP220. This interaction increases the overall signaling output of these receptors in cells.

  • 6-Mercaptopurine modulates the coactivator TRAP220 in a dose-dependent manner.
  • TRAP220 potentiates NOR-1 mediated transactivation through specific protein regions.
  • This mechanism operates independently of standard phosphorylation sites.
  • The study focuses on molecular interactions within cell cultures.
low2005-05-01 · Annals of the New York Academy of Sciences

Engineering a dopaminergic phenotype in stem/precursor cells: role of Nurr1, glia-derived signals, and Wnts.

Arenas E

This review outlines how Nurr1, glial signals, and Wnt proteins guide stem cells to become dopamine neurons, a process critical for improving future cell replacement therapies in Parkinson's disease. It highlights current limitations in integrating these engineered cells into the brain to avoid side effects like dyskinesia.

  • Stem cells offer standardized candidates for dopamine cell replacement therapy in Parkinson's disease.
  • Nurr1 and retinoid X receptors drive the differentiation and survival of dopamine neuron precursors.
  • Glia and Wnt proteins significantly influence the proliferation and development of dopamine neurons.
  • Current stem-cell grafts struggle with functional integration and risk causing dyskinesias in patients.