Identification and Validation of Inverse Agonists for Nuclear Receptor Subfamily 4 Group A Member 2.
Tian L, Lin Y, Cheng C, Yang H, Qiu X, Li S, Jia C, Le W
Researchers identified a compound called K-strophanthoside that suppresses the activity of the NR4A2 protein in laboratory settings. This molecule binds directly to the protein and reduces its transcriptional function, acting as an inverse agonist.
- K-strophanthoside is a new chemical tool that inhibits NR4A2 activity.
- The compound binds to specific amino acids in the NR4A2 ligand-binding domain.
- It mimics the effects of reducing NR4A2 levels in cell studies.
- This work provides a potential target for disorders involving excessive NR4A2 function.
Saikosaponin A, a bioactive compound from Bupleuri radix, protects dopaminergic neurons and correlates with NURR1 expression in 6-hydroxydopamine-injected hemi-Parkinsonian mouse model.
Huh E, Choi Y, Kim JH, Lee S, Oh MS
Saikosaponin A protects dopaminergic neurons and increases NURR1 expression in a mouse model of Parkinson's disease. This preclinical study suggests a potential mechanism for neuroprotection but does not involve human patients or NR4A2-specific genetic variants.
- Saikosaponin A reduces neuronal damage in mice with Parkinson-like symptoms.
- The compound correlates with increased NURR1 expression in dopaminergic neurons.
- This is a preclinical animal study, not human clinical evidence.
- NR4A2 variants are not specifically studied or targeted in this research.
Distinct endothelial gene responses to acute exercise in skeletal muscle.
Addington AK, Wall RM, Wei X, Frate SD, Olsen ML, Drake JC, Craige SM
This study identifies Nr4a2 as one of the early genes activated in endothelial cells (blood vessel lining) during acute exercise in mice. It characterizes how these specific cells respond to physical stress by altering gene expression related to blood flow and metabolism, distinct from the response in muscle fibers themselves.
- Nr4a2 activates in mouse endothelial cells immediately after acute exercise.
- Endothelial cells show a unique gene signature compared to skeletal muscle fibers.
- The study uses specialized mouse technology to isolate blood vessel cell responses.
- Findings highlight roles in angiogenesis, oxidative stress, and vascular remodeling.
- Results provide insight into how blood vessels adapt to physiological stress.
Evaluating SH-SY5Y cells as a dopaminergic neuronal model: morphological, transcriptomic, and proteomic insights.
Işlek Camadan EE, Sarihan M, Kasap M, Akpinar G, Koçyiğit E
This study evaluates the stability and maturity of SH-SY5Y neuroblastoma cells as a model for Parkinson's disease research. The differentiated cells show transient expression of dopaminergic markers and require continuous external stimuli to maintain their state, suggesting they do not fully replicate mature neurons.
- SH-SY5Y cells differentiate into neuron-like forms using a specific chemical protocol.
- Dopaminergic markers like Nurr1 appear but show asynchronous and transient expression patterns.
- Cells require continuous external stimuli to maintain their differentiated state.
- The model lacks the stability and functional maturity of true mature neurons.
Computational association in parkinson's disease SNPs with brain structural and functional alterations.
Subramaniyan S, Kuriakose BB, Nattan V, Alhazmi AH, Wong LS, Muthusamy K
This study uses computer modeling to predict how Parkinson's disease-related genetic variants affect protein structure and drug binding. It identifies specific mutations in the NURR1 gene that may alter its function and suggests potential FDA-approved drugs might bind to these altered proteins.
- The research relies entirely on computational simulations, not human or animal experiments.
- It analyzes nine Parkinson's genes, including NURR1, for harmful genetic variants.
- Molecular docking predicts how specific drugs interact with mutant proteins in silico.
- No clinical data or patient outcomes are reported in this study.
Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression.
Chawla A, Cakmakci D, Fiori LM, Zang W, Maitra M, Yang J, Żurawek D, Frosi G, Rahimian R, Mitsuhashi H, Davoli MA, Denniston R, Chen GG, Yerko V, Mash D, Girdhar K, Akbarian S, Mechawar N, Suderman M, Li Y, Nagy C, Turecki G
This study links major depression to specific genetic changes in brain cells, identifying NR4A2 as a key transcription factor active in neurons affected by the disorder. It demonstrates that depression-associated DNA variants disrupt NR4A2 binding sites, potentially altering synaptic communication in deep-layer excitatory neurons.
- NR4A2 binds to regulatory regions in neurons linked to major depression risk.
- Depression genetic variants disrupt these NR4A2 binding sites in human brain tissue.
- The study uses single-nucleus profiling of over 200,000 cells from human donors.
- Microglia also show altered chromatin accessibility related to immune regulation in depression.
Conspecifics confer survival advantage in the face of night-light polluted environment: Evidence from melatonin secretion, sleep, mood and cognitive performance in Indian house crows.
Buniyaadi A, Bhardwaj SK, Kumar V
Living with other crows helps Indian house crows cope better with nighttime light pollution, improving mood and brain function without changing melatonin or sleep. This social support may be a key survival strategy in noisy, disrupted environments.
- Group living reduces depression-like behavior in crows under light pollution
- Social interaction boosts problem-solving and cognitive performance
- No change in melatonin or sleep patterns despite improved mood
- Brain gene changes suggest enhanced neural plasticity and reduced inflammation
- Social support may be an evolutionary survival mechanism
Carboxylic Acid Bioisosteres Boost Nurr1 Agonist Selectivity.
Stiller T, Gege C, Saeb W, Vietor J, López-García Ú, Busch R, Kohlhof H, Vitt D, Merk D
Researchers modified a drug candidate to selectively activate the Nurr1 protein without affecting other enzymes, demonstrating that this selective activation promotes neuroprotective gene expression in dopaminergic cells. This work provides a more specific tool for studying Nurr1 biology but does not involve human trials or direct treatment of NR4A2-related syndromes.
- The study creates a selective Nurr1 agonist by removing unwanted DHODH inhibition from vidofludimus.
- The new compound shows over 100-fold selectivity for Nurr1 compared to the original drug.
- Treatment of dopaminergic cells induces genes linked to neuroprotection and neuronal health.
- This is preclinical chemistry work with no human clinical data or patient outcomes.
Neuroprotective role of Nigella Sativa seed oil in mitigating bisphenol a-induced neurodegeneration.
Hatipoglu D, Burak Ates M, Senturk G, Koca O, Bulut A, Donmez N
Nigella Sativa seed oil reduces brain and nerve damage caused by bisphenol A (BPA) in rats by boosting protective genes like NR4A2, reducing inflammation and cell death, and improving antioxidant levels. This suggests NSO may help protect the nervous system from environmental toxins.
- NSO boosts NR4A2, a gene linked to brain health
- NSO reduces brain and nerve damage from BPA
- NSO lowers inflammation and cell death markers
- NSO increases antioxidants like glutathione
- Findings suggest NSO could protect against toxin-induced neurodegeneration
NR4A2 attenuates early brain injury after intracerebral hemorrhage by promoting M2 microglial polarization via TLR4/TRAF6/NF-κB pathway inhibition.
Hu D, Huang C, Tang L, Lei J, Wang J, Hu W, Chen M, Song S, Lu L, Xu P
This study shows that NR4A2 protects brain tissue in rats after bleeding by reducing inflammation and strengthening the blood-brain barrier. The protein works by shifting immune cells to a healing state and blocking specific inflammatory signals.
- NR4A2 levels drop significantly in rat brains following hemorrhage.
- Boosting NR4A2 reduces bleeding volume and improves neurological outcomes.
- The protein promotes anti-inflammatory M2 microglial polarization.
- NR4A2 blocks the TLR4/TRAF6/NF-κB inflammatory pathway.
- Blocking this pathway negates the protective effects of NR4A2.
Berberine mitigates colitis-associated neuroinflammation and anxiety through modulation of the AMPK/NURR1 pathway.
Habiba ES, Fathelbab MH, AbdElaziz MM, El-Sayed NS, Mady MM, Khamis GM
Berberine reduces anxiety and gut inflammation in rats with colitis by activating the AMPK/NURR1 pathway. This preclinical study demonstrates that modulating NURR1 can alleviate neuroinflammation associated with intestinal disease.
- Study uses a rat model of colitis, not humans or NR4A2 patients.
- Berberine lowers anxiety-like behaviors and gut inflammation in treated rats.
- Mechanism involves upregulating AMPK and NURR1 expression in colon tissue.
- Results are preclinical; no clinical trials or human data are presented.
Nurr1 modulators - a patent review (2019-present).
Egner M, Merk D
This review catalogs recent patents for small molecules that activate the Nurr1 protein, which is relevant to NR4A2-related syndromes. It highlights ongoing efforts to develop drugs for neurodegenerative diseases and cancer but notes significant gaps in experimental validation for many of these compounds.
- Patents cover synthetic and natural ligands targeting Nurr1 modulation.
- Proposed uses focus on neurodegeneration and cancer treatment.
- Many claimed ligands lack sufficient experimental validation.
- Some patent claims are overly broad without supporting data.
Exploring the genetic characteristics of overweight-related osteoarthritis using machine learning.
Jiang Z, Xu C, Shi W, Lin Z, Li H, Zhang H, Li Z
This study identifies NR4A2 as one of six genes associated with osteoarthritis in overweight patients using machine learning analysis of human tissue data. The research focuses on joint health and inflammation rather than the neurological or developmental aspects of NR4A2-related syndromes.
- NR4A2 appears in a diagnostic model for osteoarthritis linked to body weight.
- The study analyzes gene expression in human cartilage and meniscus tissue.
- It connects NR4A2 to DNA replication, inflammation, and epigenetic changes.
- No findings relate to dopaminergic neurons or NR4A2 syndrome phenotypes.
Comparative transcriptomic analyses of macrophages infected with Toxoplasma gondii strains of different virulence provide molecular insights into the response of macrophage in phagocytosis and polarization to infection.
Zhu S, Liu J, Xu K, Xu F, Jiang Y, Dai L, Pei T, Zhu Y, Liu D, Zhang X, Xu J, Yang J, Pan Z, Tao J, Hou Z
The study found that different strains of Toxoplasma gondii alter macrophage function in distinct ways, with one strain (YZ-1) strongly boosting immune activity by increasing the expression of key genes like Nr4a2 and Il6, enhancing macrophage phagocytosis and promoting an inflammatory M1 state. These findings highlight Nr4a2 as a central player in macrophage responses during infection.
- Nr4a2 is upregulated during Toxoplasma infection and linked to immune activation
- The YZ-1 strain boosts macrophage phagocytosis and M1 polarization
- Il6 and Nr4a2 are central genes in the macrophage response network
- Different Toxoplasma strains affect macrophages in unique ways
- These findings may reveal new targets for treating toxoplasmosis
Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.
López-García Ú, Vietor J, Marschner JA, Heering J, Morozov V, Wein T, Merk D
Researchers identified the specific binding site and mechanism by which vidofludimus activates the NR4A2 protein, allowing them to design a more potent version of this drug. This structural insight provides a foundation for creating better synthetic activators of NR4A2 in the future.
- Vidofludimus binds to an allosteric pocket on the NR4A2 protein.
- Activation involves dimer dissociation and coregulator release.
- Structure-guided design created a more potent NR4A2 agonist.
- The study focuses on molecular mechanics, not clinical outcomes.
Chromatin accessibility and transcriptomic profiles of sheep pituitary function associated with fecundity.
Li S, Zhao B, Chen P, Cai Y, Xu H, Yan C, Wang F, Zhang Y
This study found that changes in chromatin structure and gene activity in sheep pituitary glands are linked to fertility differences. It identified NR4A2 and other key genes that may control hormone release involved in reproduction.
- NR4A2 is a potential regulator of pituitary hormone secretion in sheep
- Chromatin changes affect genes tied to reproductive hormone control
- Key genes like CMKLR1 and TAFA1 may influence fertility
- Findings could help improve reproductive efficiency in sheep
Expression of HDAC3-Y298H Point Mutant in Medial Habenula Cholinergic Neurons Has No Effect on Cocaine-Induced Behaviors.
Alizo Vera V, Childs JE, Kim J, Matheos DP, Wood MA
Changing a specific HDAC3 enzyme in brain cells linked to addiction did not affect cocaine-related behaviors in mice, suggesting HDAC3 may not play a key role in these processes in the medial habenula.
- HDAC3 mutation in addiction-related brain cells had no effect on cocaine behaviors
- Results contradict earlier expectations about HDAC3's role in addiction
- Findings suggest other pathways may be more important in addiction relapse
- No impact on cocaine-seeking or reward-related behaviors in mice
Alpha-Synuclein drives NURR1 and NLRP3 Inflammasome dysregulation in Parkinson's disease: From pathogenesis to potential therapeutic strategies.
Abdelaziz AM
This review explains how alpha-synuclein aggregates disrupt NURR1 function and trigger inflammatory responses in Parkinson's disease. It highlights the molecular mechanisms linking protein misfolding, neuroinflammation, and dopaminergic neuron loss.
- Alpha-synuclein aggregates damage neurons by disrupting mitochondria and lysosomes.
- These aggregates activate the NLRP3 inflammasome, driving harmful neuroinflammation.
- Reduced NURR1 activity increases vulnerability to oxidative stress and toxicity.
- The paper is a review of mechanisms, not a clinical study or trial.
Expression of Prooncogenic Nuclear Receptor 4A (NR4A)-Regulated Genes β1-Integrin and G9a Inhibited by Dual NR4A1/2 Ligands.
Zhang L, Gatlin V, Gupta S, Salinas ML, Romero S, Cai JJ, Chapkin RS, Safe S
Dual inhibitors of NR4A1 and NR4A2 reduce the expression of specific genes in colon cancer cells by blocking these receptors from binding to DNA. This study demonstrates that chemical compounds can simultaneously target both NR4A1 and NR4A2 proteins to alter gene activity in a cellular model.
- Compounds block NR4A1 and NR4A2 from activating target genes in cancer cells.
- The study uses colon cancer cell lines, not human patients or animal models.
- No evidence is provided regarding neurological development or dopaminergic function.
- The findings do not translate to current treatment options for NR4A2 syndrome.
Correction: Molecular basis of ligand-dependent Nurr1-RXRα activation.
Yu X, Shang J, Kojetin DJ
This paper details the molecular mechanism by which Nurr1 and RXRα proteins interact to activate gene expression when bound to specific ligands. It provides structural insights into how these transcription factors function together at the cellular level.
- The study focuses on the molecular basis of ligand-dependent activation of Nurr1-RXRα complexes.
- It describes protein-protein interactions without testing treatments in humans or animal models.
- No clinical data, patient outcomes, or therapeutic trials are reported.
Development of In Vitro Parkinson's Disease Model Mediated by MPP+ and α-Synuclein Using Wharton's Jelly Mesenchymal Stem Cells.
Gamit N, Patil M, Soumya BS, Dharmarajan A, Warrier S
This study creates a laboratory model of Parkinson's disease using stem cells to mimic the loss of dopaminergic neurons. It demonstrates that toxic agents can reduce Nurr1 levels and cause cell death in these cells, providing a tool for drug screening. This work does not provide clinical evidence or treatment options for NR4A2-related syndromes.
- Researchers differentiated stem cells into dopaminergic neurons expressing Nurr1.
- Toxic agents reduced Nurr1 expression and caused neuronal cell death in the model.
- The model serves as a cost-effective tool for screening potential Parkinson's therapies.
- No human patients or NR4A2 genetic variants were studied in this research.
Mitigating Diabetic Cardiomyopathy: The Synergistic Potential of Sea Buckthorn and Metformin Explored via Bioinformatics and Chemoinformatics.
Safavi K, Abedpoor N, Hajibabaie F, Kaviani E
This study found that combining sea buckthorn extract and metformin works better than either treatment alone in protecting the hearts of mice with diabetes-related heart disease. The combination reduced inflammation, oxidative stress, and cell death in the heart, partly by regulating genes like NR4A2 that are involved in ferroptosis and metabolic health.
- Sea buckthorn and metformin together protect the heart in diabetic mice
- NR4A2 is among key genes involved in the heart damage process
- The combo reduces inflammation and cell death more effectively than single treatments
- Targeting ferroptosis may help treat diabetic heart disease
- Results suggest a promising new approach for managing heart complications in diabetes
Satb2 and Nr4a2 are required for the differentiation of cortical layer 6b.
Zhao L, Tao YC, Hu L, Liu XY, Zhang Q, Zhang L, Ding YQ, Song NN
This study uses mouse models to show that the Nr4a2 protein works alongside Satb2 to help specific early-born neurons in the cerebral cortex develop correctly. Deleting Nr4a2 disrupts this developmental process, confirming its essential role in forming cortical layer 6b neurons during brain growth.
- Nr4a2 and Satb2 cooperate to drive the differentiation of early-born cortical neurons.
- Deleting Nr4a2 alters gene expression patterns required for normal layer 6b development.
- Satb2 deletion increases Nr4a2 levels, suggesting complex regulatory interactions between these factors.
- The research relies entirely on mouse models and does not involve human patients or treatments.
Increased NaV1.2 expression and its interaction with CaM contribute to the hyperexcitability induced by prolonged inhibition of CaMKII.
Liang H, Qin L, Feng R, Shim J, Huang X, Xu X, Zhao D, Yu Z, Boczek T, Li M, Tong Y, Huang J, Gao Q, Wang L, Cao X, Liu D, Du K, Xu J, Zhao Y, Wang W, Seehus CR, Zhao W, Guo F
Inhibiting the enzyme CaMKII in neurons causes hyperexcitability and seizure-like activity by reducing NR4A2 levels, which leads to an overexpression of the sodium channel NaV1.2. This excessive sodium channel activity is driven by increased binding between NaV1.2 and calmodulin, a process that can be reversed by blocking this specific interaction.
- CaMKII inhibition reduces NR4A2 expression in neurons from rats, mice, and humans.
- Lower NR4A2 levels cause increased production of the NaV1.2 sodium channel.
- Excess NaV1.2 binds more strongly to calmodulin, increasing neuronal excitability.
- Blocking the NaV12-calmodulin interaction rescues hyperexcitability in experimental models.
Towards a unified molecular mechanism for liganddependent activation of NR4A-RXR heterodimers.
Yu X, He Y, Kamenecka TM, Kojetin DJ
This study identifies a specific molecular mechanism where certain ligands cause the NR4A2 protein complex to dissociate, potentially offering a new way to target these proteins in disease. The findings suggest that current drug testing methods may need expansion to capture this alternative activation pathway. This work remains strictly at the basic science level with no direct clinical application or human data.
- Ligands can trigger NR4A2-RXR dissociation, a non-classical activation mechanism.
- Selective agonists are required to observe this dissociation effect clearly.
- The study proposes unifying this mechanism for neurodegenerative disease targeting.
- No human trials, patient data, or clinical treatments are involved.
Neurotoxic Effects of Atrazine on Dopaminergic System via miRNAs and Energy-Sensing Pathways.
Chen X, Hu X, Liu H, He J, Li Y, Zhang X
Atrazine exposure damages the dopaminergic system in rats by reducing key proteins like NURR1 and tyrosine hydroxylase while increasing alpha-synuclein. The study identifies specific microRNA and energy-sensing pathway changes that drive this neurotoxicity.
- Atrazine lowers NURR1 and tyrosine hydroxylase levels in rat brains.
- Atrazine increases alpha-synuclein, a protein linked to neuronal stress.
- The herbicide alters miRNA profiles affecting dopaminergic development.
- AMPK and mTOR pathways show significant changes during exposure.
- Findings suggest mechanisms for preventing atrazine-induced neurotoxicity.
The Organogermanium Compound 3-(trihydroxygermyl)propanoic Acid Exerts Anti-Inflammatory Effects via Adenosine-NR4A2 Signaling.
Azumi J, Takeda T, Shibata S, Shimada Y, Aso H, Nakamura T
This study identifies a mechanism where an organogermanium compound reduces inflammation by stabilizing adenosine to activate the NR4A2 pathway in immune cells. The findings are based entirely on cell culture experiments and do not involve human patients or animal models of neurological disease.
- The research uses THP-1 immune cells, not neurons or patient samples.
- It focuses on general inflammation suppression via NR4A2 signaling.
- No evidence is provided for treating NR4A2-related syndromes in humans.
- The compound targets inflammatory pathways unrelated to dopaminergic function.
NURR1 Deficiency Is Associated to Altered Microglial Phenotype in Male Mice.
Montarolo F, Thielens S, Bove M, Bertolotto A, Tempia F, Hoxha E
NURR1 deficiency in male mice reduces the number of microglial cells in the substantia nigra and alters their inflammatory gene expression without affecting dopamine neuron survival. These specific changes in brain immune cells correlate with the hyperactive and impulsive behaviors observed in the deficient mice.
- NURR1 loss lowers microglial cell counts specifically in the substantia nigra region of the brain.
- Inflammatory gene markers shift, indicating altered stress response and cellular damage signaling.
- Dopamine neuron numbers remain normal despite the behavioral changes and immune alterations.
- The study links NURR1's role in microglia directly to behavioral outcomes in mice.
Effects of culture media on gene expression in reconstructed human epidermis and THP-1 monocytes for skin sensitization evaluation in co-culture systems.
Sugimoto-Sawada Y, Yamashiro M, Kono M, Ikeda H, Itagaki H, Iijima K
The study found that NR4A2 and other genes (NR4A1, NR4A3, SIK1, HMOX1) are more strongly activated in immune cells when skin cells are exposed to a skin sensitizer, suggesting these genes could help detect skin allergies. The type of culture medium had a bigger effect on gene activity than cell-to-cell contact, but the interaction between skin and immune cells still influenced responses to irritants.
- NR4A2 increases in immune cells when skin cells are exposed to a sensitizer
- Five genes (NR4A1, NR4A2, NR4A3, SIK1, HMOX1) are strong markers for skin sensitization
- Culture medium affects gene expression more than cell co-culture
- Skin cell damage signals boost immune cell gene activity
- These genes may help detect skin allergies in testing
Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection.
Gérardin P, Medina-Santos R, Le Clerc S, Bruneau L, Maillot A, Labib T, Rahmouni M, Spadoni JL, Meyniel JP, Cornet C, Lefebvre C, El Jahrani N, Savara J, Mathew MJ, Fontaine C, Payet C, Ah-You N, Chabert C, Mussard C, Porcherat S, Medjane S, Noirel J, Marimoutou C, Hocini H, Zagury JF
This study found long-term changes in gene activity in people still suffering from chikungunya symptoms over 10 years after infection, including genes linked to immune function, nerve health, and cell metabolism. These changes suggest ongoing immune and neurological issues, possibly due to a hidden virus or increased vulnerability to other infections.
- Gene changes persist over 10 years after chikungunya infection
- Immune and nerve-related genes are significantly altered
- Findings suggest possible hidden virus or immune dysfunction
- May point to new treatment targets for chronic symptoms
Modeling amyotrophic lateral sclerosis with amniotic membrane-derived mesenchymal stem cells: A novel approach for disease modeling.
Soumya BS, Gamit N, Patil M, Shreenidhi VP, Dharmarajan A, Warrier S
This study creates an in-vitro model of ALS using stem cells to screen for drugs, rather than investigating NR4A2-related syndromes. The researchers induced ALS-like symptoms in motor neurons and observed that the NURR1 gene expression increased alongside oxidative stress. This work provides a platform for drug testing in ALS but offers no direct insights into treatment or mechanisms for NR4A2 conditions.
- The study models ALS, not NR4A2-related syndromes or Parkinson's disease.
- NURR1 expression rises as a secondary effect of induced oxidative stress in this model.
- No human data, clinical trials, or specific NR4A2 therapies are evaluated.
- The findings apply to general ALS drug screening, not the child's condition.
Identification of NR4A2 as a Potential Predictive Biomarker for Atherosclerosis.
Yuan L, Bai R, Han X, Xiang J
NR4A2 is elevated in atherosclerotic plaques and strongly linked to immune cells involved in the disease, suggesting it could help diagnose or monitor atherosclerosis. This finding highlights NR4A2 as a potential biomarker for a common cardiovascular condition.
- NR4A2 levels rise in atherosclerotic plaques
- NR4A2 correlates with immune cells like macrophages and B cells
- Machine learning identified NR4A2 as a top candidate biomarker
- Validation confirmed higher NR4A2 in disease tissue
- May help diagnose or track atherosclerosis progression
Embryonic exposure to valproic acid and neonicotinoid deteriorates the hyperpolarizing GABA shift and impairs long-term potentiation of excitatory transmission in the local circuit of intermediate medial mesopallium of chick telencephalon.
Matsushima T, Toji N, Wada K, Shikanai H, Izumi T
Exposure to valproic acid or imidacloprid during embryonic development disrupts normal brain circuitry and impairs learning in chicks. These chemicals downregulate NR4A2 along with other transcriptional regulators, leading to impaired synaptic plasticity that can be partially rescued by specific ion channel blockers.
- Embryonic exposure to valproic acid or imidacloprid impairs learning and memory in chicks.
- These exposures disrupt GABA signaling and impair long-term potentiation in brain circuits.
- Both chemicals downregulate NR4A2 and other transcriptional regulators in the developing brain.
- Bumetanide rescues impaired synaptic plasticity caused by valproic acid exposure.
- The study uses chick models to investigate environmental impacts on neurodevelopment.
Discovery of Endothelial-Monocyte Crosstalk in Ischemic-Reperfusion Injury Following Liver Transplantation Based on Integration of Single-Cell RNA and Transcriptome RNA Sequencing.
Sun C, Li L, Li D, Wang Z
This study investigates liver injury during transplantation and identifies NR4A2 as a gene upregulated in immune cells called monocytes. The research focuses on how these immune cells interact with liver blood vessel cells to worsen inflammation, using patient data and mouse models. It does not address brain development, neurological symptoms, or potential treatments for NR4A2-related syndromes.
- NR4A2 appears in monocytes during liver ischemia-reperfusion injury, not in neural contexts.
- The study links NR4A2 to immune-mediated inflammation in the liver.
- Findings rely on mouse models and human liver tissue, not neurological phenotypes.
- No connection is made to dopaminergic neurons or neurodevelopmental outcomes.
Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice.
Park JH, Mok J, Park S, Kim D, Kang MS, Park TS, Park J
This study shows that celecoxib improves muscle strength and metabolism in mice by activating a specific receptor pathway. The research focuses entirely on skeletal muscle physiology and does not address the dopaminergic neuron loss or movement disorders associated with NR4A2-related syndromes.
- Celecoxib activates PROKR1 signaling to increase oxidative muscle fibers in mice.
- Prenatal celecoxib exposure improves lean mass and grip strength in offspring.
- The drug enhances mitochondrial content and fatty acid oxidation in muscle tissue.
- NR4A2 levels rise as a downstream effect of PROKR1 activation in this context.
- The study investigates skeletal muscle, not the brain pathways affected by NR4A2.
Contribution of the dopaminergic system in toxoplasmic encephalitis neuroimmunopathogenesis.
Anteplıoğlu T, Dincel GC, Alçiğir ME, Bışkın Türkmen M, Yapici TS, Kul O, Al-Olayan E, Alshahrani MY, El-Ashram S
This study examines how a parasitic brain infection alters dopamine-related proteins in mice, finding that while one production enzyme increases, key receptors and transporters decrease. The research focuses on the biological mechanisms of toxoplasmic encephalitis rather than NR4A2-related genetic syndromes or human clinical outcomes.
- The study uses infected mice, not humans or patients with NR4A2 variants.
- It investigates Toxoplasma gondii infection, a parasitic disease unrelated to genetic neurodevelopmental disorders.
- Findings describe protein expression changes in mouse brain tissue during chronic infection.
- No clinical data, treatment trials, or genotype-phenotype correlations for NR4A2 are presented.
Luteolin ameliorates rat model of metabolic syndrome-induced cardiac injury by apoptosis suppression and autophagy promotion via NR4A2/p53 regulation.
Dai X, Liang B, Sun Y
Luteolin protects rat hearts from metabolic syndrome damage by regulating NR4A2 to reduce cell death and improve cellular cleanup. This study uses an animal model of heart disease, not a human condition related to NR4A2 syndromes.
- Study tests luteolin in rats with metabolic syndrome, not NR4A2-related disorders.
- NR4A2 regulates heart cell survival and cleanup pathways in this animal model.
- Luteolin reduces inflammation and stress markers in rat hearts.
- No human data or direct link to NR4A2 genetic syndromes is provided.
Overexpression of FTO alleviates traumatic brain injury induced posttraumatic epilepsy by upregulating NR4A2 expression via m6A demethylation.
Xiao M, Wang X, Xiao E, Ming Q
This study shows that increasing FTO protein levels reduces epilepsy and brain damage in mice after traumatic brain injury by stabilizing NR4A2 mRNA. The mechanism involves FTO removing methyl groups from NR4A2, which prevents its degradation and allows it to protect neurons.
- FTO overexpression reduces seizure frequency and neuronal damage in mouse models of post-traumatic epilepsy.
- FTO upregulates NR4A2 by removing m6A marks, preventing the mRNA from being degraded.
- Blocking NR4A2 reverses the protective effects of FTO, confirming it is a key downstream target.
- The findings suggest targeting the FTO-NR4A2 axis could treat epilepsy following brain injury.
Bioinformatics-driven identification and validation of hub genes regulating endometriosis-related infertility within human granulosa cells.
Luo J, Wang H, Zhou L, Wang J, Song M, Cheng Y, Rao M, Zhao S, Tang L
This study identifies NR4A2 as one of five hub genes in human granulosa cells associated with endometriosis-related infertility, but it does not investigate its role in neurodevelopment or motor function. The research focuses on using BTG2, another identified gene, as a biomarker for predicting oocyte quality and IVF outcomes rather than addressing the child's condition.
- NR4A2 is identified as a hub gene in granulosa cells from patients with endometriosis.
- The study links BTG2 expression levels to oocyte retrieval rates and blastocyst formation.
- No findings relate to NR4A2's function in the brain, dopamine pathways, or motor control.
- The research is limited to reproductive biology and infertility outcomes.
WITHDRAWN: Overexpression of NR4A2 Alleviates Renal and Myocardial Injury in Diabetic Nephropathy in Rats Through the HDAC11/ SPRY1 Pathway.
Xu J, Li J, Xu X, Zhu H, Zhang X, Yang M, Ren Y
This paper has been withdrawn and is not available for review. No reliable data or conclusions can be provided.
- The study was withdrawn by the publisher
- No valid results or findings are available
- The paper cannot be used for clinical or research decisions