The Selective Agonist for Sphingosine-1-Phosphate Receptors Siponimod Increases the Expression Level of NR4A Genes in Microglia Cell Line.
Montarolo F, Martire S, Marnetto F, Valentino P, Valverde S, Capobianco MA, Bertolotto A
The multiple sclerosis drug siponimod increases NR4A2 gene expression in microglia cells in a laboratory setting. This finding identifies a potential molecular mechanism for the drug's protective effects in the central nervous system.
- Siponimod boosts NR4A2 levels specifically in microglial brain cells.
- The effect does not occur in blood cells or oligodendrocytes.
- This is an in vitro study using cell lines, not human patients.
- NR4A2 functions as an anti-inflammatory gene in this context.
Role of Nuclear-Receptor-Related 1 in the Synergistic Neuroprotective Effect of Umbilical Cord Blood and Erythropoietin Combination Therapy in Hypoxic Ischemic Encephalopathy.
Choi JW, Kang SJ, Choi JI, Kwack K, Kim M
This study identifies Nurr1 (NR4A2) as a key mediator of neuroprotection in a mouse model of neonatal brain injury treated with umbilical cord blood and erythropoietin. The combination therapy activates the Wnt/beta-catenin signaling pathway, which upregulates Nurr1 to reduce brain damage.
- Researchers used a mouse model of neonatal hypoxic-ischemic encephalopathy.
- Combination therapy with umbilical cord blood and erythropoietin reduced brain infarct size.
- Nurr1 expression increased significantly in treated mice compared to untreated controls.
- The Wnt/beta-catenin pathway activation drives Nurr1-mediated neuroprotection.
- Findings are preclinical and do not involve human patients or NR4A2 syndrome.
Integration of transcriptomics and metabolomics provides metabolic and functional insights into reduced insulin secretion in MIN6 β-cells exposed to deficient and excessive arginine.
Xu L, Lin X, Li X, Hu Z, Hou Q, Wang Y, Wang Z
This study uses mouse pancreatic beta cells to show that abnormal arginine levels disrupt insulin secretion through metabolic stress and oxidative damage. Nr4a2 appears as one of several transcription factors involved in this cellular response, but the findings do not address neurological function or human disease mechanisms.
- The research focuses on insulin-secreting pancreatic cells, not brain neurons.
- Nr4a2 is identified incidentally among many genes affected by arginine imbalance.
- No clinical data, patient phenotypes, or treatment outcomes are reported.
- Findings describe general cellular metabolism rather than NR4A2-specific biology.
Reprogramming by Cytosolic Extract of Human Embryonic Stem Cells to Improve Dopaminergic Differentiation Potential of Human Adipose Tissue-derived Stem Cells.
Mobasseri S, Javeri A, Fakhr Taha M
This study shows that treating human fat-derived stem cells with an extract from embryonic stem cells improves their ability to become dopamine-producing neurons in a lab dish. The reprogrammed cells express higher levels of key dopaminergic markers like NURR1 and TH compared to untreated cells. This suggests a potential method for generating neural cells for future therapies, but it remains strictly preclinical.
- ESC extract reprograms fat stem cells to enhance their plasticity in vitro.
- Reprogrammed cells show increased expression of dopaminergic genes like NURR1 and TH.
- The study uses human cells but lacks any animal or human clinical testing.
- No direct link to NR4A2 syndrome treatment or current clinical trials is established.
[Protective effect of nuclear receptor related 1 (Nurr1) on nerves in rats with cerebral occlusion/reperfusion injury and its mechanism].
Hu D, Xie X, Zhang H
Overexpressing Nurr1 protects brain cells and improves neurological outcomes in rats after stroke by reducing inflammation, oxidative stress, and cell death. This study demonstrates a neuroprotective mechanism of Nurr1 in an acute injury model rather than a chronic developmental or dopaminergic context.
- Nurr1 overexpression reduces brain damage and improves neurological scores in rats after stroke.
- The protection works by lowering inflammation, oxidative stress, and apoptotic cell death signals.
- This is an acute injury model in rats, not a study of NR4A2-related syndrome or Parkinson's.
The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons.
Alsanie WF, Alhomrani M, Gaber A, Habeeballah H, Alkhatabi HA, Felimban RI, Abdelrahman S, Hauser CAE, Chaudhary AG, Alamri AS, Raafat BM, Alamri A, Anwar S, Alswat KA, Althobaiti YS, Asiri YA
Prenatal exposure to pregabalin alters the development of ventral midbrain dopaminergic neurons in mice by increasing specific gene expression and reducing ATP release, even at therapeutic doses. This suggests that pregabalin use during pregnancy may interfere with the formation and function of brain cells critical for movement and behavior.
- Pregabalin increases genes linked to dopaminergic neuron development in mouse embryos.
- Therapeutic doses reduce ATP release in developing midbrain neurons without killing them.
- The study uses primary mouse embryonic neurons, not human subjects or clinical data.
- Findings highlight potential risks of pregabalin use during pregnancy for fetal brain development.
Striatal dopaminergic neurons as a potential target for GDNF based ischemic stroke therapy.
Beker MÇ, Beker M, Çağlayan AB, Bolat B, Kılıç Ü, Torun Köse G, Kılıç E
GDNF delivery increases Nurr1 expression and reduces neuronal degeneration in a mouse model of ischemic stroke, but it does not protect or increase the number of dopaminergic neurons. This preclinical study focuses on stroke recovery mechanisms rather than NR4A2-related neurodevelopmental conditions.
- GDNF treatment increases Nurr1 expression in the ischemic striatum of mice.
- GDNF reduces neuronal degeneration but does not protect dopaminergic neurons.
- The study uses a mouse model of cerebral ischemia, not NR4A2 syndrome.
- No clinical data or human trials are reported in this paper.
Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries.
Willems S, Müller M, Ohrndorf J, Heering J, Proschak E, Merk D
Researchers designed new chemical compounds that activate the Nurr1 protein more effectively than existing templates. These novel molecules share no structural similarity to previous candidates but demonstrate superior potency in laboratory tests.
- New Nurr1 agonists show higher potency than the amodiaquine template.
- The compounds are structurally distinct from prior known activators.
- Pharmacophore modeling identified key features required for Nurr1 activation.
Genome-Wide Identification of Immune-Related Alternative Splicing and Splicing Regulators Involved in Abdominal Aortic Aneurysm.
Wu S, Liu S, Chen N, Zhang C, Zhang H, Guo X
This study found that immune-related gene splicing and splicing factors are disrupted in abdominal aortic aneurysm (AAA), with two key genes, NR4A1 and NR4A2, significantly downregulated. These genes are part of a broader network involving immune cell changes and splicing regulation, suggesting a role in disease development.
- NR4A1 and NR4A2 are downregulated in AAA
- Immune-related splicing events are altered in AAA
- Splicing factors like SF3B1 are linked to immune gene regulation
- Macrophages and plasma cells are increased in AAA
- Splicing changes distinguish AAA samples from controls
Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers.
Blondin-Ladrie L, Fourcade L, Modica A, Aranguren M, de Montigny N, Labbé AC, Alary M, Guédou F, Poudrier J, Roger M
This study identifies NR4A2 as one of several immune-related genes with altered expression in the blood monocytes of women naturally resistant to HIV infection. It does not provide information on NR4A2's role in neurodevelopment, Parkinson's disease, or any treatment options for NR4A2-related syndromes.
- NR4A2 appears as an incidental marker in an unrelated immunology study.
- The research focuses on HIV resistance in commercial sex workers.
- No findings relate to dopaminergic neurons or neurological function.
- The paper offers no clinical guidance for NR4A2-related conditions.
CB2 receptor activation inhibits the phagocytic function of microglia through activating ERK/AKT-Nurr1 signal pathways.
Han QW, Shao QH, Wang XT, Ma KL, Chen NH, Yuan YH
Activating the CB2 receptor suppresses microglial inflammation by boosting Nurr1 levels in cell culture models. This mechanism suggests that targeting this pathway could reduce neurotoxicity, but the findings are limited to laboratory cells and do not yet demonstrate clinical benefit.
- CB2 activation increases nuclear Nurr1 protein in microglial cell lines.
- Nurr1 activation inhibits the phagocytic function of microglia.
- ERK/AKT signaling pathways mediate this regulatory effect.
- Results are derived from BV-2 cells and primary midbrain microglia cultures.
- No human data or animal model efficacy is reported.
Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution.
Honkova K, Rossnerova A, Chvojkova I, Milcova A, Margaryan H, Pastorkova A, Ambroz A, Rossner P, Jirik V, Rubes J, Sram RJ, Topinka J
This study links specific air pollution exposures to changes in DNA methylation patterns in human blood, including alterations near the NR4A2 gene. These epigenetic changes are associated with pathways involved in neuronal function and neurodegenerative diseases.
- The study analyzes DNA methylation in 125 non-smoking policemen exposed to different air pollution levels.
- Researchers identified thousands of differentially methylated loci associated with specific geographic locations.
- Changes near NR4A2 link air pollution exposure to dopaminergic system and neurodegenerative disease pathways.
- Affected biological processes include neuronal functions, axon guidance, and cell adhesion.
BMS-470539 Attenuates Oxidative Stress and Neuronal Apoptosis via MC1R/cAMP/PKA/Nurr1 Signaling Pathway in a Neonatal Hypoxic-Ischemic Rat Model.
Yu S, Doycheva DM, Gamdzyk M, Gao Y, Guo Y, Travis ZD, Tang J, Chen WX, Zhang JH
This study shows that activating the MC1R receptor reduces brain damage and cell death in rats after oxygen deprivation, a process that depends on Nurr1. The drug BMS-470539 protects neurons by triggering a signaling pathway involving Nurr1, but this work is limited to animal models of stroke rather than genetic syndromes.
- BMS-470539 reduces brain injury and cell death in rats after hypoxic-ischemic events.
- Neuroprotection requires both MC1R activation and the presence of Nurr1 protein.
- CRISPR knockout of Nurr1 eliminates the drug's protective effects in this model.
- The study uses a rat model of stroke, not NR4A2-related genetic syndrome.
Overexpression of miR-200b-3p in Menstrual Blood-Derived Mesenchymal Stem Cells from Endometriosis Women.
de Oliveira RZ, de Oliveira Buono F, Cressoni ACL, Penariol LBC, Padovan CC, Tozetti PA, Poli-Neto OB, Ferriani RA, Orellana MD, Rosa-E-Silva JC, Meola J
miR-200b-3p is significantly overexpressed in menstrual stem cells from women with endometriosis, which may contribute to abnormal cell behavior and tissue implantation. This finding highlights a potential molecular mechanism in endometriosis but does not directly involve NR4A2-related syndrome.
- miR-200b-3p is overexpressed in endometriosis stem cells
- Overexpression links to increased cell proliferation and stemness
- May promote tissue implantation in endometriosis
- Not directly related to NR4A2/NURR1 syndrome
- Findings are specific to endometriosis biology
Potential role of inducible GPR3 expression under stimulated T cell conditions.
Shiraki H, Tanaka S, Guo Y, Harada K, Hide I, Yasuda T, Sakai N
This study investigates the role of GPR3 in T cell activation and its interaction with NR4A2, but it does not provide evidence relevant to NR4A2-related syndromes or dopaminergic function. The findings are limited to immune cell biology and do not translate to clinical insights for this condition.
- GPR3 expression increases in T cells after stimulation.
- NR4A2 modulation by GPR3 occurs in human T cell lines.
- Mouse models show no NR4A2 change without GPR3.
- GPR3 helps suppress effector T cell activation.
- No link to dopaminergic neurons or NR4A2 syndrome phenotypes.
Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice.
Liu L, Wang H, Chen X, Zhang Y, Li W, Rao X, Liu Y, Zhao L, Pu J, Gui S, Yang D, Fang L, Xie P
This study identifies Nr4a2 as part of a gene regulatory network in mouse brains affected by gut microbiota changes linked to depression. It does not provide evidence for treatment or understanding specific to NR4A2-related syndromes in humans.
- The research uses mice with altered gut bacteria to model depression.
- Nr4a2 appears in a gene network associated with neurodevelopmental dysfunction.
- Findings focus on inflammatory and neurodevelopmental pathways in the hippocampus.
- No human data or clinical trials for NR4A2 syndromes are included.
Synergistic Effects of Combined Nurr1 Overexpression and Natural Inducers on the More Efficient Production of Dopaminergic Neuron-Like Cells From Stem Cells.
Beiki R, Khaghani M, Esmaeili F, Dehghanian F
Overexpressing the Nurr1 gene alongside brain extract factors efficiently converts stem cells into dopaminergic neuron-like cells in a laboratory setting. This preclinical study demonstrates that combining genetic modification with specific environmental cues enhances the production of these specialized neurons from stem cell lines.
- Nurr1 overexpression combined with neonatal rat brain extract boosts dopaminergic differentiation.
- The study uses P19 stem cells, not human patient cells or clinical trials.
- Results show synergistic effects on creating neuron-like cells in vitro.
- This is basic molecular biology research with no direct human application yet.
Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.
Sharma S, Shen T, Chitranshi N, Gupta V, Basavarajappa D, Sarkar S, Mirzaei M, You Y, Krezel W, Graham SL, Gupta V
This review summarizes how Retinoid X Receptors (RXRs) regulate gene expression and influence neuroinflammation in various neurological disorders. It highlights that targeting RXRs with specific ligands shows protective effects in animal and cell models of conditions like Parkinson's disease.
- RXRs are nuclear receptors that modulate genes involved in neuronal stress and inflammation.
- Pharmacological activation of RXRs protects neurons in models of Alzheimer's and Parkinson's.
- The paper is a review of existing knowledge, not new clinical data.
- No direct link to NR4A2 genetics or specific treatments for NR4A2 syndrome is established.
LincRNA-p21 Upregulates Nuclear Orphan Receptor Nr4a2 and Aggravates Myocardial Ischemia/Reperfusion Injury via Targeting MiR-466i-5p.
Zhai X, Liu R, Li J, Wang F, Liu L, Wei S, Bian Y, Pang J, Xue M, Qin D, Wang S, Xu T, Xu F, Cao S, Yuan Q, Chen Y
This study found that a molecule called LincRNA-p21 worsens heart damage after a heart attack by reducing a protective protein called Nr4a2. The molecule works by trapping a microRNA that normally keeps Nr4a2 levels in check. Blocking LincRNA-p21 improved heart function and reduced cell death in mice and heart cells.
- LincRNA-p21 increases heart damage after a heart attack
- It reduces Nr4a2, a protective protein in heart cells
- LincRNA-p21 traps a microRNA that controls Nr4a2
- Blocking LincRNA-p21 protects heart cells and improves recovery
- This pathway could be a target for future heart attack treatments
Hydroxychloroquine improves motor function and affords neuroprotection without inhibition of inflammation and autophagy in mice after intracerebral hemorrhage.
Yoshimizu A, Kinoshita K, Ichihara Y, Kurauchi Y, Seki T, Katsuki H
Hydroxychloroquine improved motor function and protected brain cells in mice after stroke-like brain bleeding, likely by preserving nerve fiber connections, even though it didn’t reduce inflammation or autophagy as expected.
- Hydroxychloroquine improved movement and brain function after brain bleeding in mice
- It protected neurons and preserved nerve fiber structure
- Benefits occurred without blocking inflammation or autophagy
- May act through direct neuroprotection, not immune or cellular cleanup pathways
Developmental Patterning and Neurogenetic Gradients of Nurr1 Positive Neurons in the Rat Claustrum and Lateral Cortex.
Fang C, Wang H, Naumann RK
This study maps the developmental timeline and spatial organization of Nurr1-positive neurons in the rat claustrum and lateral cortex. It establishes that these specific neurons are generated sequentially during embryonic days 13.5 to 17.5, forming distinct neurogenetic gradients.
- Nurr1 expression begins as an elongated line on embryonic day 13.5 in rats.
- Most dorsal endopiriform neurons are born between days 13.5 and 14.5.
- Claustrum sub-regions form primarily between embryonic days 14.5 and 15.5.
- Deep layer cortical neurons arise from day 14.5 to 15.5.
- Superficial layer cortical neurons arise from day 15.5 to 17.5.
Exosomal lncRNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1)contributes to the progression of allergic rhinitis via modulating microRNA-511/Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) axis.
Wang T, Cai W, Wu Q, Chen D, Wang P, Xu Z
This study shows that NR4A2 promotes inflammation and cell death in nasal tissue during allergic rhinitis, suggesting it acts as a driver of this specific immune condition rather than a neurodevelopmental factor. The findings are based on human nasal epithelial cells and do not provide evidence regarding the neurological symptoms or treatment responses associated with NR4A2 syndrome.
- NR4A2 increases inflammation and cell death in nasal tissue during allergic rhinitis.
- The study uses human nasal cells, not brain tissue or animal models of neurodevelopment.
- Results focus on immune response mechanisms unrelated to dopaminergic pathways.
- No clinical data or treatment implications for NR4A2-related neurodevelopmental disorders are presented.
Nuclear receptors of NR1 and NR4 subfamilies in the regulation of microglial functions and pathology.
Katsuki H
This review summarizes how activating specific nuclear receptors, including Nurr1 (NR4A2), can reduce inflammation and improve microglial function in animal models of neurological diseases. It highlights that while these pathways show therapeutic potential for conditions like Parkinson's disease, the evidence remains preclinical and does not yet translate to human treatments.
- Nurr1 activation reduces neuroinflammation and improves outcomes in animal disease models.
- NR1 receptor agonists also show promise in treating neurological disorders in animals.
- The paper is a review of existing literature, not a new clinical study.
- No human data or direct treatment recommendations for NR4A2 syndrome are provided.
Variability in Behavioral Phenotypes after Forced Swimming-Induced Stress in Rats Is Associated with Expression of the Glucocorticoid Receptor, Nurr1, and IL-1β in the Hippocampus.
Ruiz-Sánchez E, López-Ramírez AM, Ruiz-Chow Á, Calvillo M, Reséndiz-Albor AA, Anguiano B, Rojas P
This study finds that vulnerable rats exhibit higher levels of Nurr1 protein in the hippocampus after stress compared to resilient rats. It suggests Nurr1 acts as a mediator in the biological response to acute stress rather than indicating a direct therapeutic target for NR4A2-related syndromes.
- Vulnerable rats show higher hippocampal Nurr1 protein levels after stress than resilient rats.
- Nurr1 mRNA levels do not differ significantly between vulnerable and resilient groups.
- The study links Nurr1 to stress coping mechanisms in an animal model.
- No human data or clinical implications for NR4A2 syndromes are presented.
Nr4a2 Transcription Factor in Hippocampal Synaptic Plasticity, Memory and Cognitive Dysfunction: A Perspective Review.
Català-Solsona J, Miñano-Molina AJ, Rodríguez-Álvarez J
This perspective review discusses the role of the Nr4a2 transcription factor in hippocampal synaptic plasticity and memory formation. It suggests that dysregulation of this protein may contribute to cognitive dysfunction in brain pathologies like Alzheimer's disease. The authors propose Nr4a2 as a potential therapeutic target for conditions involving cognitive decline.
- Nr4a2 regulates gene transcription essential for synaptic plasticity and memory consolidation.
- Hippocampal synaptic dysfunction linked to Nr4a2 underlies cognitive decline in disorders like Alzheimer's.
- The review highlights Nr4a2 as a potential novel therapeutic target for cognitive dysfunctions.
- Molecular mechanisms of Nr4a2 in the hippocampus remain poorly understood.
Effects of Training Status and Exercise Mode on Global Gene Expression in Skeletal Muscle.
Bizjak DA, Zügel M, Treff G, Winkert K, Jerg A, Hudemann J, Mooren FC, Krüger K, Nieß A, Steinacker JM
This study found that acute exercise, especially endurance or strength training, strongly activates NR4A2 and related genes in muscle, more so than training status. The NR4A family genes, including NR4A2, were the most upregulated in response to exercise, suggesting they play a key role in muscle adaptation. Training level had little effect on gene expression compared to the type of exercise performed.
- NR4A2 is highly activated by acute exercise in muscle
- Exercise mode (endurance vs. strength) affects gene expression more than training level
- NR4A genes are central to muscle adaptation
- Gene changes peak 3 hours after exercise
- NR4A2 may help guide personalized training strategies
NR4A2 alleviates cardiomyocyte loss and myocardial injury in rats by transcriptionally suppressing CCR5 and inducing M2 polarization of macrophages.
Miao H, Li X, Zhou C, Liang Y, Li D, Ji Q
NR4A2 protects heart cells in rats with diabetic heart disease by suppressing a specific inflammatory receptor called CCR5. This mechanism reduces harmful immune cell activity and prevents damage to heart muscle tissue.
- NR4A2 levels drop in rat hearts affected by diabetes.
- Restoring NR4A2 protects heart cells from high-sugar damage.
- NR4A2 works by turning down the CCR5 inflammatory receptor.
- This study focuses on heart injury, not brain or movement disorders.
Current Status of the Hypothesis of a Claustro-Insular Homolog in Sauropsids.
Puelles L
This paper discusses the evolutionary origins of brain structures by comparing how the gene Nr4a2 marks specific regions in birds and reptiles versus mammals. It does not provide clinical data, treatment options, or direct insights into human NR4A2-related syndromes.
- The study focuses on comparative neuroanatomy across species rather than human disease.
- Nr4a2 serves as a molecular marker for identifying homologous brain regions in birds and reptiles.
- No clinical evidence, patient data, or therapeutic strategies are presented.
- The research addresses evolutionary biology questions about pallial development.
The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells.
Wang N, Ji X, Wu Y, Zhou S, Peng H, Wang J, Yu S, Zhang J
This study compares how well astrocytes and mesenchymal stem cells convert into dopamine-producing neurons in a lab setting. It finds that astrocytes are more efficient at this conversion than stem cells when exposed to specific molecular signals.
- Astrocytes convert to dopamine neurons more efficiently than stem cells.
- The study uses only cell cultures, not animals or humans.
- It identifies different molecular requirements for each cell type.
- No clinical treatments or patient outcomes are reported.
The Distribution, Expression Patterns and Functional Analysis of NR1D1 and NR4A2 in the Reproductive Axis Tissues of the Male Tianzhu White Yak.
Dai L, Zhang Q, Shi J, Bai X, An X, Zhang B, Zhang Y, Zhao X
NR4A2 and NR1D1 are active in male yak reproductive tissues, especially in testes and Leydig cells, where they help regulate steroid and androgen production. Their expression changes with age and varies between tissues, suggesting a key role in male fertility and hormone control.
- NR4A2 is highly active in testes and Leydig cells
- NR4A2 and NR1D1 levels rise at age 6 in testes
- These receptors regulate steroid and androgen metabolism
- NR4A2 may directly influence hormone synthesis
- Expression differs across reproductive tissues
Characterization and Study of Gene Expression Profiles of Human Periodontal Mesenchymal Stem Cells in Spheroid Cultures by Transcriptome Analysis.
Suga T, Usui M, Onizuka S, Sano K, Sato T, Nakazawa K, Ariyoshi W, Nishihara T, Nakashima K
NR4A2 is highly active in 3D cultures of human periodontal stem cells and acts as a brake on bone formation. When NR4A2 is reduced, these cells produce more bone-related proteins and form larger calcified structures, suggesting NR4A2 normally suppresses bone development in this context.
- NR4A2 is strongly expressed in 3D stem cell cultures
- Reducing NR4A2 boosts bone formation markers
- NR4A2 suppresses osteogenesis in these cells
- No effect on fat or cartilage formation
- Spheroid culture enhances NR4A2's role in bone regulation
NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast.
de Alwis N, Beard S, Binder NK, Pritchard N, Kaitu'u-Lino TJ, Walker SP, Stock O, Groom KM, Petersen S, Henry A, Said JM, Seeho S, Kane SC, Tong S, Hannan NJ
This study finds that NR4A2 levels in placental tissue do not change in pregnancies complicated by growth restriction or preeclampsia, despite higher levels being found in the blood of these patients. The research suggests that circulating NR4A2 likely originates from outside the placenta, as experimental hypoxia only reduced NR4A2 in isolated cells and did not alter key placental growth factors.
- Placental NR4A2 expression remains unchanged in preterm growth restriction and preeclampsia cases.
- Circulating NR4A2 transcripts are elevated in these pregnancies, suggesting a non-placental source.
- Hypoxia reduces NR4A2 only in isolated cytotrophoblast cells, not in whole placental tissue.
- Silencing NR4A2 in cells alters stress and inflammatory genes but not angiogenic factors.
The Possible Protective Role of Dark Chocolate Against Acrylamide Neurotoxicity in Weaning Rats Cerebellum.
Hassan DM, Welson NN, Yassa HD
Dark chocolate may protect the developing brain from damage caused by acrylamide, a chemical found in some cooked foods, by boosting levels of a key brain-protective gene called NR4A2. In rats, dark chocolate reduced brain cell damage and helped restore gene activity linked to nerve health.
- Dark chocolate reduced brain cell damage from acrylamide
- NR4A2 gene expression increased with dark chocolate
- Acrylamide harms developing brain cells
- Dark chocolate may help protect against dietary toxins
- Findings suggest a possible protective dietary strategy
Development and Profiling of Inverse Agonist Tools for the Neuroprotective Transcription Factor Nurr1.
Zaienne D, Willems S, Schierle S, Heering J, Merk D
Researchers developed chemical tools that block the Nurr1 protein's activity in cell cultures. These compounds reduce the expression of genes controlled by Nurr1 and alter inflammatory responses in astrocytes. This work provides new laboratory instruments to study how Nurr1 functions in disease models.
- Indole-based inverse agonists block Nurr1 transcriptional activity by over 90%.
- Compounds disrupt Nurr1 homodimers and displace corepressor proteins.
- Treatment mimics the effects of silencing the NR4A2 gene in cells.
- Reduced Nurr1 activity lowers interleukin-6 release in human astrocytes.
- These tools help probe Nurr1 roles in neuroinflammation and cancer research.
The Impact of CB1 Receptor on Nuclear Receptors in Skeletal Muscle Cells.
Haddad M
Stimulating CB1 receptors in skeletal muscle cells increases the expression of NR4A1 and NR4A3 genes, while blocking these receptors reduces the expression of NR4A1, NR4A2, and NR4A3. This study identifies a molecular link between cannabinoid signaling and NR4A family gene regulation in muscle tissue. The findings do not provide clinical evidence or treatment options for NR4A2-related syndromes.
- CB1 receptor stimulation increases NR4A1 and NR4A3 mRNA in skeletal muscle cells.
- Blocking CB1 receptors decreases NR4A1, NR4A2, and NR4A3 expression.
- The study uses mouse muscle cell lines, not human patients or animal models of disease.
- No clinical relevance to NR4A2 syndrome symptoms or treatment is established.
α-Synuclein Induces the GSK-3-Mediated Phosphorylation and Degradation of NURR1 and Loss of Dopaminergic Hallmarks.
García-Yagüe ÁJ, Lastres-Becker I, Stefanis L, Vassilatis DK, Cuadrado A
This study explains how alpha-synuclein, a protein linked to Parkinson's disease, triggers the destruction of NURR1 through a specific phosphorylation pathway. It identifies the exact region of the NURR1 protein that is targeted for degradation by GSK-3 kinase.
- Alpha-synuclein activates GSK-3 kinase to phosphorylate NURR1.
- Phosphorylation marks NURR1 for ubiquitination and proteasomal degradation.
- Amino acids 123-134 of NURR1 are the specific target site.
- This mechanism explains NURR1 loss in synucleinopathies like Parkinson's.
Selymatra: A web application for protein-profiling analysis of mass spectra.
Nardone D, Ciaramella A, Cerreta M, Pulcrano S, Bellenchi GC, Leone L, Manco G, Febbraio F
This paper describes a software tool for analyzing mass spectrometry data to identify proteins, rather than providing new medical insights or treatments. The application was tested using cells that overexpress the NURR1 protein to demonstrate its ability to detect tagged versions of the receptor. It does not offer clinical guidance or evidence regarding NR4A2-related syndromes.
- The study presents a web application for automated protein identification from mass spectra.
- Researchers validated the tool using cells overexpressing a tagged NURR1 receptor.
- The software compares sample and control spectra to predict likely proteins.
- No clinical data, patient outcomes, or treatment effects are reported.
- The work is purely computational and methodological with no therapeutic relevance.
A systematic dissection of human primary osteoblasts in vivo at single-cell resolution.
Gong Y, Yang J, Li X, Zhou C, Chen Y, Wang Z, Qiu X, Liu Y, Zhang H, Greenbaum J, Cheng L, Hu Y, Xie J, Yang X, Li Y, Bai Y, Wang YP, Chen Y, Tan LJ, Shen H, Xiao HM, Deng HW
This study maps the different types of bone-forming cells in humans and identifies a rare subtype that produces high levels of NR4A2. It confirms that human bone cells differ significantly from mouse bone cells, highlighting the limitations of using mice to understand human biology.
- Researchers identified three distinct subtypes of human osteoblasts using single-cell sequencing.
- A rare osteoblast subtype serves as the primary source of NR4A2 in bone tissue.
- The study reveals significant transcriptional differences between human and mouse osteoblasts.
- Preosteoblasts and a rare subtype regulate angiogenesis and blood cell formation.
- Findings emphasize the need for human-specific models over mouse models for bone research.
Minireview: What is Known about SUMOylation Among NR4A Family Members?
Dodat F, Mader S, Lévesque D
This review explains how SUMOylation, a chemical modification of proteins, regulates the activity of NR4A family transcription factors including NURR1. It details the molecular mechanisms by which this process influences cellular functions such as inflammation and neuronal health without proposing specific treatments for patients.
- NR4A receptors are orphan nuclear receptors lacking known endogenous ligands.
- SUMOylation dynamically regulates NR4A transcriptional activity and function.
- The review covers impacts on cell cycle, apoptosis, and inflammation.
- No clinical data or treatment implications for NR4A2 syndrome are presented.
Reconstruction of the Cytokine Signaling in Lysosomal Storage Diseases by Literature Mining and Network Analysis.
Parolo S, Tomasoni D, Bora P, Ramponi A, Kaddi C, Azer K, Domenici E, Neves-Zaph S, Lombardo R
This study uses computational analysis to map inflammatory signaling pathways in three lysosomal storage diseases, identifying NR4A2 as a potential regulator of cytokine production in Gaucher disease. The research highlights complex inflammatory networks that may serve as targets for future anti-inflammatory therapies in these conditions.
- NR4A2 appears as a candidate regulator in the monocyte cytokine network for Gaucher disease.
- The study focuses on sphingolipid accumulation disorders, not NR4A2-related syndromes.
- Findings are based on literature mining and network analysis, not experimental validation.
- No human clinical data or treatment outcomes for NR4A2 variants are presented.