Expression profiling suggests the involvement of hormone-related, metabolic, and Wnt signaling pathways in pterygium progression.
Li J, Tao T, Yu Y, Xu N, Du W, Zhao M, Jiang Z, Huang L
This study found that pterygium, a eye condition that can affect vision, involves abnormal activity in hormone-related, metabolic, and Wnt signaling pathways. It identified nine key genes, including NR4A2, that are either overactive or underactive in pterygium tissue and may play a role in disease development.
- NR4A2 is downregulated in pterygium tissue
- Wnt and metabolic pathways are overactive
- Nine genes, including SPP1 and MYH11, are potential targets
- Findings may guide future treatments
- Results are from human tissue in a Chinese population
Transfer of neuron-derived α-synuclein to astrocytes induces neuroinflammation and blood-brain barrier damage after methamphetamine exposure: Involving the regulation of nuclear receptor-associated protein 1.
Huang J, Ding J, Wang X, Gu C, He Y, Li Y, Fan H, Xie Q, Qi X, Wang Z, Qiu P
Methamphetamine exposure causes neurons to transfer alpha-synuclein to astrocytes, which suppresses Nurr1 and triggers neuroinflammation that damages the blood-brain barrier. Restoring Nurr1 levels or blocking alpha-synuclein transfer reduces this damage in animal models.
- Methamphetamine drives alpha-synuclein from neurons into astrocytes, causing brain inflammation.
- This process lowers Nurr1 levels, leading to blood-brain barrier leakage and injury.
- Increasing Nurr1 or blocking alpha-synuclein transfer protects the blood-brain barrier in mice.
- The study focuses on drug-induced toxicity, not NR4A2-related developmental syndromes.
Neuropilin-1 (NRP1) expression distinguishes self-reactive helper T cells in systemic autoimmune disease.
Raveney BJ, El-Darawish Y, Sato W, Arinuma Y, Yamaoka K, Hori S, Yamamura T, Oki S
This study identifies Neuropilin-1 (NRP1) as a marker for self-reactive T cells that drive systemic autoimmune diseases like lupus. Researchers find that reducing these specific T cells improves symptoms in mouse models and that humans with lupus also show increased levels of NRP1-positive T cells.
- NRP1 marks self-reactive helper T cells in autoimmune disease models.
- Reducing NRP1+ T cells ameliorates lupus-like symptoms in mice.
- Human lupus patients show significantly increased peripheral NRP1+ T cells.
- Nr4a2 deficiency reduces self-reactive responses but spares normal immune function.
Identification of diagnostic biomarkers and therapeutic targets in peripheral immune landscape from coronary artery disease.
Feng X, Zhang Y, Du M, Li S, Ding J, Wang J, Wang Y, Liu P
This study identified 14 immune-related genes in blood that can help diagnose advanced coronary artery disease, with NR4A2 among them. The gene NR4A2 was linked to immune and inflammatory processes in atherosclerosis, suggesting it may play a role in disease progression.
- NR4A2 is a potential blood biomarker for advanced coronary artery disease
- The 14-gene model shows strong diagnostic accuracy
- NR4A2 may influence inflammation and cholesterol handling in blood vessels
- IL13RA1, another gene in the model, affects key pathways in atherosclerosis
- Findings suggest possible new treatment targets for heart disease
Potential of immune-related genes as promising biomarkers for premature coronary heart disease through high throughput sequencing and integrated bioinformatics analysis.
Wang H, Shao J, Lu X, Jiang M, Li X, Liu Z, Zhao Y, Zhou J, Lin L, Wang L, Xu Q, Chen Y, Zhang R
NR4A2 is part of a network of genes linked to immune dysfunction in premature coronary heart disease, suggesting it could serve as a biomarker for early detection and potential treatment target, though the findings are not directly about NR4A2-related syndrome in children.
- NR4A2 is part of a gene network tied to immune issues in early heart disease
- The study identifies NR4A2 as a hub gene in a potential biomarker network
- Immune cell changes, including CD4 T cells and neutrophils, are linked to premature heart disease
- NR4A2 may be a target for future therapies or diagnostics
- Findings are based on adult heart disease, not pediatric NR4A2 syndrome
Dopaminergic Neurons Differentiated from LRRK2 I1371V-Induced Pluripotent Stem Cells Display a Lower Yield, α-Synuclein Pathology, and Functional Impairment.
Jagtap S, Potdar C, Yadav R, Pal PK, Datta I
Dopaminergic neurons derived from stem cells with the LRRK2 I1371V mutation show reduced production, impaired function, lower synaptic connectivity, and increased toxic alpha-synuclein buildup, indicating early developmental and functional deficits linked to Parkinson’s disease.
- LRRK2 I1371V mutation reduces dopaminergic neuron yield
- Mutant neurons show weaker dopamine release and calcium response
- Increased alpha-synuclein clumping and phosphorylation
- Fewer synaptic connections and lower maturity markers
- Deficits begin early, at the floor plate cell stage
Association Between Circulating CD4+ T Cell Methylation Signatures of Network-Oriented SOCS3 Gene and Hemodynamics in Patients Suffering Pulmonary Arterial Hypertension.
Benincasa G, Maron BA, Affinito O, D'Alto M, Franzese M, Argiento P, Schiano C, Romeo E, Bontempo P, Golino P, Berrino L, Loscalzo J, Napoli C
This study found that changes in DNA methylation of the SOCS3 gene in immune cells are strongly linked to heart function measures in pulmonary hypertension patients, with lower methylation tied to better heart output and lower pressure in the right heart. SOCS3 levels were also higher in patients' blood, suggesting it may play a role in disease progression and could help predict outcomes.
- SOCS3 gene methylation levels correlate with heart function in PAH patients
- Lower SOCS3 methylation links to better cardiac output and lower right heart pressure
- SOCS3 is overactive in PAH patients' blood cells
- This is the first study linking immune cell methylation to hemodynamics in PAH
- SOCS3 may serve as a blood-based biomarker for PAH severity
Transcriptomic analysis in the striatum reveals the involvement of Nurr1 in the social behavior of prenatally valproic acid-exposed male mice.
Kim H, Woo RS, Yang EJ, Kim HB, Jo EH, Lee S, Im H, Kim S, Kim HS
This study shows that reducing Nurr1 levels in the striatum of mouse models improves social deficits and synaptic health, suggesting a potential therapeutic target for neurodevelopmental conditions. However, the findings are based entirely on animal models and do not provide evidence for human treatments or clinical outcomes.
- Reducing Nurr1 in mouse striatum rescues social deficits and synaptic abnormalities.
- Nurr1 levels are elevated in two different ASD mouse models.
- A known Nurr1 ligand mimics these deficits in healthy mice.
- The study uses prenatal valproic acid exposure to induce ASD-like symptoms in mice.
- No human data, clinical trials, or direct relevance to NR4A2 variants is presented.
Bioinformatics analysis of mRNA profiles and identification of microRNA-mRNA network in CD4+ T cells in seasonal allergic rhinitis.
Jin P, Zhang H, Zhu X, Sun K, Jiang T, Shi L, Zhi L, Zhang H
This study analyzes gene expression in immune cells from patients with seasonal allergies and identifies NR4A2 as one of the few genes consistently altered during allergy seasons. The findings focus on immune system mechanisms like neutrophil activation rather than neurological development or function. This research does not provide information relevant to understanding or treating NR4A2-related neurodevelopmental syndromes.
- NR4A2 appears as a differentially expressed gene in CD4+ T cells during seasonal allergies.
- The study focuses on immune responses, specifically neutrophil activation and degranulation.
- No neurological, developmental, or dopaminergic mechanisms are investigated.
- Results suggest potential targets for allergy treatment, not neurodevelopmental disorders.
The Role of NR4A1 in the Pathophysiology of Osteosarcoma: A Comprehensive Bioinformatics Analysis of the Single-Cell RNA Sequencing Dataset.
Liu W, Hao Y, Tian X, Jiang J, Qiu Q
This study found that NR4A1, not NR4A2, is linked to worse outcomes in osteosarcoma patients, with higher NR4A1 levels tied to shorter survival, metastasis, and resistance to chemotherapy. The analysis used single-cell data to show NR4A1 is more active in certain tumor cells during disease progression.
- NR4A1 levels are higher in metastatic and recurrent osteosarcoma
- High NR4A1 predicts shorter survival in osteosarcoma patients
- NR4A1 is linked to chemotherapy resistance
- NR4A2 expression did not correlate with survival in this study
- NR4A1 may serve as a prognostic marker in osteosarcoma
Identification of Immune Microenvironment Changes and the Expression of Immune-Related Genes in Liver Cirrhosis.
Liu Y, Dong Y, Wu X, Wang X, Niu J
This study analyzes liver tissue from patients with cirrhosis to understand how immune cells change during the disease. It identifies NR4A2 as one of four transcription factors that may regulate natural killer (NK) cell activity in the liver.
- NR4A2 appears in liver tissue data alongside other immune-regulating transcription factors.
- The research focuses on liver cirrhosis, not neurological development or function.
- No clinical data or treatment implications for NR4A2-related syndromes are presented.
A Novel Mechanism of Coactivator Recruitment by the Nurr1 Nuclear Receptor.
Daffern N, Radhakrishnan I
This study identifies a specific structural mechanism by which the Nurr1 protein binds to coactivators, revealing how it regulates gene transcription. It shows that a short segment of Nurr1 forms a helix to dock into a groove on the SRC1 protein, a process shared with other transcription factors like STAT6. This work provides fundamental molecular biology insights but does not offer direct clinical guidance or treatment options for NR4A2-related syndromes.
- Nurr1 uses a specific helix segment to bind directly to the SRC1 coactivator protein.
- This binding occurs in a hydrophobic groove shared with other transcription factors like STAT6.
- The research details basic molecular mechanics of gene regulation without clinical application.
- Findings do not translate to immediate therapeutic strategies for NR4A2-related conditions.
NURR1 expression regulates retinal pigment epithelial-mesenchymal transition and age-related macular degeneration phenotypes.
Yao PL, Parmar VM, Choudhary M, Malek G
This study investigates the role of NURR1 in age-related macular degeneration, a common eye disease affecting vision in older adults. It finds that activating NURR1 can protect retinal cells from damage and improve function in mouse models of the disease.
- NURR1 protects retinal pigment epithelial cells from transitioning into scar-like tissue.
- An activator drug improved vision and reduced inflammation in mouse eye models.
- The research focuses on AMD, a distinct condition unrelated to NR4A2-related syndromes.
Medicinal Chemistry and Chemical Biology of Nurr1 Modulators: An Emerging Strategy in Neurodegeneration.
Willems S, Merk D
This review summarizes current knowledge about small molecules that interact with the Nurr1 protein and discusses their potential role in treating neurodegenerative diseases. It highlights that while structural insights are improving, high-quality chemical tools for controlling Nurr1 are still lacking, meaning target validation is incomplete.
- Nurr1 has neuroprotective and anti-inflammatory properties relevant to neurodegeneration.
- Several small molecule ligands targeting Nurr1 have been identified recently.
- High-quality chemical tools for pharmacological control of Nurr1 are currently insufficient.
- Target validation for Nurr1 as a therapeutic strategy remains pending.
Recruitment of the CoREST transcription repressor complexes by Nerve Growth factor IB-like receptor (Nurr1/NR4A2) mediates silencing of HIV in microglial cells.
Ye F, Alvarez-Carbonell D, Nguyen K, Leskov K, Garcia-Mesa Y, Sreeram S, Valadkhan S, Karn J
This study shows that Nurr1 (NR4A2) directly suppresses HIV transcription in human microglial cells by recruiting repressor complexes to the viral DNA. The findings suggest that activating Nurr1 could potentially silence HIV and reduce neuroinflammation in the brain.
- Nurr1 binds directly to HIV DNA to block viral transcription in human microglia.
- Activating Nurr1 enhances HIV silencing, while reducing it allows viral expression.
- Nurr1 recruits repressor complexes to shut down both HIV and inflammatory genes.
- The research focuses on HIV latency mechanisms, not NR4A2-related syndrome treatments.
Transcriptome landscapes that signify Botrylloides leachi (Ascidiacea) torpor states.
Hyams Y, Panov J, Rosner A, Brodsky L, Rinkevich Y, Rinkevich B
This study analyzes the molecular changes in a marine colonial animal during periods of dormancy, identifying NR4A2 as one of many genes that become more active when the organism is inactive. The research focuses on general survival mechanisms and tissue regeneration in this non-mammalian species rather than human neurological development or disease. It provides no information about NR4A2-related syndromes in children.
- Study examines torpor in a marine colonial animal, not humans or mammals.
- NR4A2 is one of 233 upregulated genes during the dormant state.
- Research focuses on general survival and regeneration mechanisms.
- No clinical data, human genetics, or therapeutic implications are presented.
- Findings do not translate to understanding NR4A2-related neurodevelopmental disorders.
Prolonged cardiac NR4A2 activation causes dilated cardiomyopathy in mice.
Ashraf S, Taegtmeyer H, Harmancey R
Prolonged activation of the NR4A2 gene in heart muscle cells causes severe heart failure and death in mice. This occurs because NR4A2 forces adult heart cells to re-enter the cell cycle without dividing, leading to cell death and structural damage.
- NR4A2 overexpression in mouse hearts leads to dilation, hypertrophy, and fatal heart failure.
- The protein triggers a fetal-like metabolic switch and disassembles heart muscle structures.
- Heart cells attempt to divide but fail, causing multinucleation and subsequent cell death.
- This study focuses exclusively on cardiac tissue, not the nervous system or NR4A2 syndrome.
A Nurr1 ligand C-DIM12 attenuates brain inflammation and improves functional recovery after intracerebral hemorrhage in mice.
Kinoshita K, Yoshimizu A, Ichihara Y, Ushida K, Kotani S, Kurauchi Y, Seki T, Katsuki H
The Nurr1 ligand C-DIM12 reduces brain inflammation and improves functional recovery in mice after intracerebral hemorrhage by suppressing microglial activation and iNOS expression. This preclinical study demonstrates that targeting Nurr1 can protect neurons and preserve axonal transport, suggesting a potential mechanism for neuroprotection.
- C-DIM12 is a Nurr1 ligand that reduces brain inflammation in mice after hemorrhage.
- Treatment improves neurological function and prevents neuron loss in the affected brain area.
- The drug suppresses microglial activation and inflammatory mediators like IL-6.
- Effects involve suppressing iNOS induction, linking Nurr1 signaling to anti-inflammatory outcomes.
- This is a mouse model study with no human clinical data or trials reported.
Regulatory Role of miRNAs and lncRNAs in Gout.
Shu J, Chen M, Ya C, Yang R, Li F
This study identifies a network of non-coding RNAs involved in gout, a condition unrelated to NR4A2-related syndrome. The findings focus on gene regulation in inflammation and immune response, not on neurodevelopmental or neurological disorders. NR4A2 appears in the network but as part of a broader inflammatory pathway, not in the context of its role in brain development or disease.
- NR4A2 is part of a gout-related RNA network
- No link to NR4A2-related neurodevelopmental syndrome
- Findings relate to inflammation, not brain function
- No therapeutic implications for NR4A2 patients
- Study is about gout, not neurogenetic disorders
Effects of bis (2-butoxyethyl) phthalate on adrenocortical function in male rats in puberty partially via down-regulating NR5A1/NR4A1/NR4A2 pathways.
Liu M, Chen H, Dai H, Wang Y, Li J, Tian F, Li Z, Ge RS
Exposure to the chemical BBOP reduces steroid hormone production in male rats by suppressing NR4A2 and related pathways. This study demonstrates that environmental toxins can disrupt adrenal function through mechanisms involving NR4A2, but it does not address neurodevelopmental outcomes or treatments for NR4A2 syndrome.
- BBOP exposure lowers corticosterone and aldosterone levels in pubertal male rats.
- The chemical down-regulates NR4A2 expression alongside other steroidogenesis genes.
- Mechanisms involve reduced AKT/ERK signaling and increased oxidative stress.
- Findings are limited to rat adrenal glands and do not inform human neurodevelopment.
The role of NURR1 in metabolic abnormalities of Parkinson's disease.
Al-Nusaif M, Yang Y, Li S, Cheng C, Le W
This review discusses how the NURR1 protein influences cellular metabolism and contributes to Parkinson's disease pathology. It highlights potential links between metabolic changes and NURR1 function as areas for future therapeutic research.
- NURR1 regulates dopaminergic neuron development and cellular metabolism.
- Metabolic abnormalities are linked to Parkinson's disease progression.
- The paper reviews existing evidence on NURR1's role in disease pathogenesis.
- Potential therapeutic implications of targeting metabolic pathways are discussed.
Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation.
Pulcrano S, De Gregorio R, De Sanctis C, Lahti L, Perrone-Capano C, Ponti D, di Porzio U, Perlmann T, Caiazzo M, Volpicelli F, Bellenchi GC
This study identifies a molecular switch in developing mouse brains that controls when the Nurr1 protein is produced to help dopamine neurons mature. The research shows that specific microRNAs delay Nurr1 expression until the right developmental stage, ensuring proper neuron formation.
- The mechanism was discovered using mouse brain development models and cell cultures.
- MicroRNAs 204/211 act as a timing switch for the Nurr1 gene.
- This regulation ensures dopamine neurons differentiate at the correct developmental stage.
- No human data or clinical treatments are involved in this research.
Nurr1 Is Not an Essential Regulator of BDNF in Mouse Cortical Neurons.
Abdollahi M, Fahnestock M
This study finds that Nurr1 does not regulate BDNF in mouse cortical neurons, contradicting its known role in other brain regions. The research relies entirely on animal cell models and offers no direct clinical insights for NR4A2-related syndromes.
- Nurr1 fails to control BDNF expression in mouse cortical neurons despite increasing both proteins.
- The study uses only mouse primary cortical neurons and pharmacological agents.
- Results suggest Nurr1's regulatory role is specific to midbrain and cerebellar cells, not the cortex.
- No human data or clinical relevance for NR4A2 patients is presented.
Transcriptome Profiling and Network Analysis Provide Insights Into the Pathogenesis of Vulvar Lichen Sclerosus.
Wang L, Lv Q, Guo J, Wang J, Pan J
This study analyzes vulvar lichen sclerosus, a skin condition unrelated to NR4A2-related syndromes. It finds that NR4A2 is downregulated in affected tissue alongside other immune and cell cycle genes. The research focuses on dermatological pathogenesis rather than neurological development or treatment for NR4A2 disorders.
- Study investigates vulvar lichen sclerosus, a chronic inflammatory skin disease.
- NR4A2 is downregulated in lesions alongside other NR4A family genes.
- Findings relate to T cell activation and reduced cell proliferation in skin.
- No connection to neurodevelopment, dopamine pathways, or pediatric care.
γ-Glutamylcysteine attenuates amyloid-β oligomers-induced neuroinflammation in microglia via blocking NF-κB signaling pathway.
Bi A, Wang Y, Chen L, Yin Z, Luo L
γ-Glutamylcysteine reduces brain inflammation caused by toxic amyloid-beta proteins by blocking a key inflammatory pathway and boosting protective proteins in brain immune cells. It also lowers oxidative stress and shows protective effects in animal models of Alzheimer's disease.
- γ-Glutamylcysteine reduces brain inflammation from amyloid-beta
- It blocks NF-κB, a major inflammation trigger
- It boosts Nurr1, a protective protein linked to brain health
- It lowers oxidative stress and supports antioxidant defenses
- It shows promise in animal models of neurodegeneration
Steroid nuclear receptor coactivator 2 controls immune tolerance by promoting induced Treg differentiation via up-regulating Nr4a2.
Zhang W, Cao X, Zhong X, Wu H, Feng M, Gwack Y, Isakov N, Sun Z
This study identifies a mechanism in the immune system where SRC2 promotes regulatory T cell development by activating the Nr4a2 gene. The findings are based entirely on mouse models and do not provide direct evidence for human treatment or NR4A2-related syndrome management.
- SRC2 activates Nr4a2 to promote regulatory T cell differentiation in mice.
- Mice lacking SRC2 develop autoimmune symptoms and severe inflammation.
- The mechanism involves SRC2 binding to the Nr4a2 promoter via NFAT1.
- This research focuses on immune tolerance, not dopaminergic neuron function.
CREB Inactivation by HDAC1/PP1γ Contributes to Dopaminergic Neurodegeneration in Parkinson's Disease.
Xu X, He X, Zhang Z, Chen Y, Li J, Ma S, Huang Q, Li M
Researchers identify a mechanism in Parkinson's disease where the CREB protein is inactivated, leading to reduced levels of NURR1 and subsequent loss of dopamine-producing neurons. Disrupting this interaction restores NURR1 levels and protects neurons in mouse models.
- CREB inactivation reduces NURR1 expression in Parkinson's patient brains.
- HDAC1/PP1γ complex causes CREB dephosphorylation, impairing neuron survival.
- Blocking this interaction restores NURR1 and protects neurons in mice.
- Study focuses on general Parkinson's pathology, not NR4A2-specific genetics.
Expression Profile of mRNAs and miRNAs Related to the Oxidative-Stress Phenomenon in the Ishikawa Cell Line Treated Either Cisplatin or Salinomycin.
Januszyk S, Mieszczański P, Lurka H, Sagan D, Boroń D, Grabarek BO
This study found that NR4A2 and several other genes change in response to chemotherapy-induced oxidative stress in endometrial cancer cells, and their activity is likely controlled by specific microRNAs. These changes may help monitor oxidative stress severity, but the findings are in cancer cells, not in people with NR4A2-related syndrome.
- NR4A2 levels change under chemotherapy stress in cancer cells
- NR4A2 is linked to miRNAs that may regulate its activity
- These changes could help track oxidative stress in cancer
- Findings are from cancer cell studies, not human NR4A2 syndrome
- No direct relevance to NR4A2-related neurodevelopmental conditions
Prenatal Hypoxia Affects Nicotine Consumption and Withdrawal in Adult Rats via Impairment of the Glutamate System in the Brain.
Stratilov VA, Vetrovoy OV, Tyulkova EI
Prenatal oxygen deprivation increases nicotine addiction risk in adult rats by altering glutamate signaling in the brain's reward system. This study identifies specific molecular changes in dopamine and glutamate pathways that drive this behavioral shift.
- Prenatal hypoxia predisposes adult rats to higher nicotine consumption.
- Withdrawal symptoms are more severe in prenatally stressed rats.
- Glutamate signaling, not dopamine levels, drives the addiction phenotype.
- Increased glutamate terminals target Nurr1-positive neurons in the VTA.
Nuclear receptor NOR-1 (Neuron-derived Orphan Receptor-1) in pathological vascular remodelling and vascular remodelling.
Ballester-Servera C, Cañes L, Alonso J, Puertas L, Taurón M, Rodríguez C, Martínez-González J
This review describes how NR4A2 and related proteins regulate blood vessel changes in heart and lung diseases. It does not provide information on NR4A2-related syndrome or treatments for children.
- NR4A2 helps control cell survival and inflammation in blood vessels.
- The paper focuses on atherosclerosis, aneurysms, and pulmonary hypertension.
- It is a review of vascular biology mechanisms.
- No clinical data or pediatric relevance is presented.
Yeast beta-glucan mediates histone deacetylase 5-induced angiogenesis in vascular endothelial cells.
Choi M, Lee SM, Lee JW, Kim I, Pack CG, Ha CH
Yeast beta-glucan promotes blood vessel formation by activating HDAC5, which turns on genes involved in angiogenesis, including NR4A2. Blocking HDAC5 stops this process, showing that beta-glucan works through this specific pathway.
- Beta-glucan triggers blood vessel growth via HDAC5 activation
- HDAC5 moves to the cell's cytoplasm when stimulated by beta-glucan
- NR4A2 is turned on as part of this pro-angiogenic process
- Blocking HDAC5 stops beta-glucan’s effect on blood vessel formation
- Beta-glucan may be a potential therapy for conditions needing new blood vessels