Environmental PFOA exposure and the risk of metabolic dysfunction-associated steatotic liver disease: An integrated computational toxicology and multi-omics study.
Zhang T, Yuan Y, Lin C, Song C, Liao T, Sun Y, Tang H
This study identifies NR4A2 as a key gene affected by environmental pollution (PFOA) in liver disease models, but it does not provide information relevant to NR4A2-related syndrome or its neurological symptoms. The research focuses on metabolic liver dysfunction rather than the dopaminergic neuron loss central to this child's condition. Consequently, the findings offer no direct clinical guidance for managing NR4A2 syndrome.
- NR4A2 appears as a hub gene in liver disease models exposed to PFOA pollution.
- The study links environmental toxins to metabolic liver dysfunction via NR4A2 pathways.
- Research focuses on hepatic steatosis, not neurological or dopaminergic outcomes.
- No human clinical data or treatment implications for NR4A2 syndrome are presented.
Keloid transcriptomics reveal heterogeneity in fibroblast subtype enrichment, gene expression, and immune cell responses
Panzer JJ, Pan M, Nair M, Loveless IM, Adrianto I, Huang L, Chitale D, Francescone R, Vendramini-Costa DB, de Guzman Strong C, Levin AM, Jones LR
This study analyzes skin tissue from keloid patients to understand how different cell types contribute to abnormal scarring. It identifies specific changes in fibroblast and immune cell populations that drive the disease process.
- Researchers analyzed RNA from keloid and normal skin tissues of 14 patients.
- The study mapped differences in fibroblast subtypes and immune cell enrichment.
- NR4A2 showed significant differential expression after adjusting for cell type composition.
- Findings reveal complex interactions between fibroblasts and immune cells in keloids.
Role of nuclear receptor NR4A2 in prolactin secretion by female rat lactotrophs.
Terashima R, Fujimoto W, Tani T, Shintani A, Kurusu S, Kawaminami M
This study shows that NR4A2 regulates prolactin release in rat pituitary cells, acting at the level of hormone secretion rather than gene transcription. The findings are limited to basic endocrine physiology in rats and do not address dopaminergic neuron survival or motor symptoms relevant to NR4A2 syndrome.
- NR4A2 knockdown reduces prolactin secretion without affecting its mRNA levels in rat pituitary cells.
- NR4A1 and NR4A3 do not significantly regulate prolactin release in this model.
- Dopaminergic inhibition suppresses the coordinated changes in Nr4a expression and prolactin secretion.
- The research focuses on endocrine function, not the dopaminergic pathways affected in NR4A2 syndrome.
From Bile Acids to a Gas-Producing Microbiome Phenotype: A Novel Mechanism of Host–Microbiome Communication
Strus M, Kasperski T, Mech K, Szczepanik A, Golińska E
This study investigates how gut bacteria produce gases in response to bile acids and how those gases affect human intestinal and pancreatic cells. It identifies NR4A2 as one of many genes whose expression changes when these bacterial gases interact with epithelial cells, but it does not address NR4A2-related syndrome or its treatment.
- Bile acids alter the amount of gas produced by specific gut bacteria.
- These bacterial gases change gene expression in human intestinal and pancreatic cells.
- NR4A2 appears as one of many genes affected by this signaling pathway.
- The research focuses on pancreatitis and general cell biology, not neurological development.
Hippocampal GDNF signaling modulation by high-intensity interval swimming and gallic acid in an animal model of Parkinson's disease.
Moghadasi M, Abdollahi S, Edalatmanesh MA, Motl RW, Najafi P, Salehi O
This study shows that high-intensity swimming and gallic acid modulate NURR1 and related signaling pathways in rats with Parkinson's-like symptoms. The findings are limited to animal models and do not provide direct evidence for human treatment or clinical outcomes.
- The study uses a rat model of Parkinson's disease, not humans.
- High-intensity swimming increased NURR1 expression in rat brains.
- Gallic acid had minimal effect on NURR1 signaling compared to exercise.
- No human clinical data or patient outcomes are reported.
- The paper focuses on molecular mechanisms in rodents.
A Non-Canonical Effector Transcriptional Programme Characterises IFN-γ– Mediated Hyperinflammation in MIS-C
Bizjan BJ, Kovač J, Tesovnik T, Šket R, Debeljak M, Avramovič MZ, Emeršič N, Vrhovšek B, Sabolić I, Smole A, Avčin T
This study identifies a specific immune pathway driving inflammation in MIS-C, a condition unrelated to NR4A2 syndrome. It finds that NR4A2 is not involved in the exhaustion of T cells during this inflammatory response and does not identify any genetic predisposition linked to the NR4A2 gene.
- The study focuses on MIS-C, an immune disorder triggered by SARS-CoV-2 infection.
- NR4A2 is mentioned only to show it is absent in the specific T-cell state observed.
- No genetic link between NR4A2 variants and MIS-C susceptibility was found.
- The research proposes JAK inhibitors as potential treatments for MIS-C inflammation.
NOR1 loss relates to inflammation and biological ageing in multiple sclerosis motor cortex.
Unlu Kobya B, Avery A, DeLuca G, Pansieri J
This study finds that reduced levels of the related protein NR4A3 in specific brain layers correlate with increased inflammation and aging markers in multiple sclerosis patients. The findings suggest that preserving this protein family's activity might help protect neurons, but the research focuses on a different disease and does not involve human trials for NR4A2-related syndrome.
- NR4A3 levels drop in deep brain layers of multiple sclerosis patients.
- Lower NR4A3 correlates with higher inflammation and aging markers.
- The study examines multiple sclerosis, not NR4A2-related syndrome.
- No human clinical data or treatment trials are included.
- Findings suggest a general neuroprotective role for this protein family.
USP13-SKP2-P57/kip2 Axis Mediates Spautin-1 Induced Transcriptional Upregulation of NURR1: Implications for NURR1 Mediated Neurotrophic Activity.
Edward A, Puttapaka SN, Vulli A, Kalivendi SV
A drug called spautin-1 increases levels of the NURR1 protein in cells and mice by blocking a specific molecular pathway. This increase in NURR1 promotes the growth of dopamine neuron extensions and improves biochemical markers in a mouse model of Parkinson's disease.
- Spautin-1 raises NURR1 levels by inhibiting the USP13-SKP2-P57/kip2 protein axis.
- NURR1 is required for spautin-1 to stimulate dopamine neuron growth in cell cultures.
- The drug improves biochemical signs of Parkinson's disease in living mice.
- This study uses only cell lines and mouse models, not human patients.
Rotenone Exposure in Zebrafish Parkinson's Disease Model Reveals NURR1-TOP2B Dysregulation and Gut-Brain Axis-Associated Pathology.
Bathurutheen DA, Raja S, Sayuti NSA, Mustapha M, Damodaran T
Rotenone exposure in zebrafish causes Parkinson's-like symptoms and gut-brain axis damage, accompanied by a decrease in Nurr1 levels. This model confirms that environmental toxins can trigger the specific molecular dysregulation seen in NR4A2-related syndromes.
- Rotenone reduces Nurr1 expression in both brain and intestine of zebrafish.
- The study links gut pathology to brain dysfunction via the gut-brain axis.
- Zebrafish serve as a model for environmental toxin-induced neurodegeneration.
- No human data or clinical treatment implications are presented.
The Cavβ4 subunit of Cav1.2 channels antagonizes isoproterenol-induced hypertrophy in rat cardiac muscle cells by down-regulating miR-183-5p.
Carrillo ED, Galicia E, García MC, Sánchez JA
This study shows that the Cavβ4 protein helps protect heart cells from stress-induced enlargement by regulating specific molecular pathways involving NR4A2. The findings are based entirely on rat heart cell experiments and do not address neurological development or human health outcomes relevant to NR4A2 syndrome.
- Cavβ4 prevents heart cell enlargement in rat models by modulating miR-183-5p levels.
- NR4A2 protein levels increase when Cavβ4 is active, suggesting a protective cellular role.
- The research focuses exclusively on cardiac muscle biology in rats.
- No human data or neurological implications for NR4A2-related disorders are presented.
SPI1 Promotes TNF-α-Induced Epithelial-Mesenchymal Transition-Like Changes in Retinal Pigment Epithelial Cells: Implications for the Pathogenesis of Age-Related Macular Degeneration.
Zhang X, Liu H
This study identifies a molecular pathway in eye cells where the protein SPI1 reduces levels of NURR1, contributing to age-related macular degeneration. It does not provide evidence regarding NR4A2 function in neurodevelopment or potential treatments for children with NR4A2-related syndromes.
- SPI1 increases ALKBH5, which lowers NURR1 levels in retinal cells.
- NURR1 reduction promotes cell changes linked to vision loss in AMD.
- The findings focus on eye disease mechanisms, not brain development.
- No clinical data or treatment implications for NR4A2 disorders are presented.
Mesenchymal stem cell-derived exosome NR4A2 inhibits fracture healing in aged rat by blocking NELL2-mediated osteogenic differentiation.
Ye P, Bai R, Ding X, Chen H, Bai Z, Wu L
This study shows that NR4A2 delays bone fracture healing in aged rats by blocking a specific signaling pathway required for new bone formation. The mechanism involves exosomes from aged stem cells carrying NR4A2, which suppresses the NELL2 gene and prevents osteogenic differentiation. This finding is specific to skeletal repair in an aging animal model and does not address the neurological or developmental aspects of NR4A2 syndrome.
- NR4A2 inhibits bone healing by suppressing the NELL2 gene in aged rats.
- Exosomes from aged stem cells deliver NR4A2 to inhibit osteogenesis.
- The study focuses on skeletal repair, not neurological development.
- Findings are limited to an animal model of aging and fracture.
- No relevance to human neurodevelopmental phenotypes or current treatments.
Machine learning-based identification of lactate metabolism-associated biomarkers in non-alcoholic fatty liver disease.
Wang X, Wang X, Zhao L, Song L
This study identifies NR4A2 as one of eight genes associated with lactate metabolism in non-alcoholic fatty liver disease (NAFLD). The research suggests that NR4A2 acts as a protective factor, meaning its downregulation is linked to the progression of liver disease in mouse models.
- NR4A2 is identified as a potential protective gene against NAFLD progression.
- The study focuses on liver disease, not neurological conditions or NR4A2-related syndromes.
- Five genes including NR4A2 show protective effects in animal models of fatty liver.
- Machine learning algorithms screened these biomarkers from existing gene expression datasets.
A eutherian-specific metaviral gene, RTL6 , coordinates microglial inflammatory responsiveness and state regulation
Ishino F, Irie M, Shiura H, Kohda T, Kaneko-Ishino T
This study shows that the gene RTL6 regulates how brain immune cells (microglia) respond to inflammation and change their functional state. It identifies NR4A2 as one of several genes influenced by this process, but it does not investigate NR4A2's specific role or any potential treatments for NR4A2-related syndromes.
- RTL6 helps brain immune cells sense inflammation and adjust their activity levels.
- Loss of RTL6 reduces the activation of NR4A2 and other immediate-early genes.
- The research focuses on microglial biology, not dopaminergic neurons or motor symptoms.
- No human data or clinical relevance to NR4A2 syndrome is presented.
Transcriptomic profiling of subpopulations of mouse embryonic subplate neurons.
Achiwa H, Hara Y, Kawaji H, Oshima M, Kaneko N, Morioka A, Hoerder-Suabedissen A, Molnár Z, Ohtaka-Maruyama C
This study maps the genetic activity of early-developing mouse brain neurons to understand how cortical circuits form. It identifies NR4A2 as a marker for specific subplate neuron subtypes during embryonic development. The findings provide a molecular framework for classifying these transient neuronal populations.
- Researchers analyzed gene expression in developing mouse subplate neurons using advanced sequencing techniques.
- The study identified ten distinct clusters of subplate neurons with unique genetic signatures.
- NR4A2 serves as a key marker for specific subplate neuron subtypes in the embryonic cortex.
- Transcriptional profiles shift rapidly between embryonic days 15 and 17, indicating dynamic development.
- The work establishes a molecular basis for distinguishing transient from persistent neuronal populations.
Correction: Nurr1 deficiency orchestrates a coupled liver-gut pathological axis revealed by multi-omics and deep-learning histopathology.
Faisal S, Ullah I, Kambey PA, Malik A, Ejaz MA, Shah SA, Li YX
This study identifies a pathological connection between the liver and gut driven by Nurr1 deficiency, using multi-omics and deep learning to analyze tissue samples. The findings focus on systemic metabolic and immune dysregulation rather than neurological outcomes relevant to NR4A2-related syndromes.
- Nurr1 deficiency links liver and gut pathology through a coupled axis.
- Research uses multi-omics and deep learning histopathology for analysis.
- Focus is on systemic metabolic and immune mechanisms, not neurodevelopment.
- No clinical data or treatment implications for NR4A2 children are presented.
Synovium-Restricted Armored PD-1-Targeted CAR-T Cells Reprogram Immunity and Resolve Experimental Arthritis
Gur C, Ravkaie L, Sharet-Eshed R, Shalita R, Avellino R, Rauchbach E, Xie K, David E, Yagel G, Zada M, Yehuda MB, Mazuz K, Locquenghien MNV, Peleg H, Naparstek Y, Atlan K, Kfir-Erenfeld S, Kuznetsov Y, Tzemach R, Lidar M, Balbir-Gurman A, Phan TS, Freitag K, Amit I
Researchers engineered T cells to target and eliminate specific immune cells in the joints of arthritis models, using NR4A2 as a safety switch to restrict activity to inflamed tissue. This approach aims to reduce inflammation locally while minimizing systemic side effects in autoimmune conditions.
- NR4A2 drives a biosensor restricting CAR-T cell activity to inflamed synovium.
- The therapy targets PD-1 on pathogenic T cells in rheumatoid arthritis models.
- Treatment reduces joint inflammation and promotes tissue-repairing immune states.
- This is preclinical work in animal models of autoimmune disease, not human trials.
Xifeng Zhichou decoction mitigates tic disorder on juvenile rats by regulating neuroinflammation and neurotransmitter homeostasis: dual modulation of Nr4a2 and gut microbiota.
Wu R, Peng J, Zhang M, He Q, Luo J, Long Q, Xiao X, Li S, Wan L
This study shows that a Chinese herbal formula reduces tic-like behaviors in juvenile rats by lowering brain inflammation and balancing neurotransmitters. The treatment works partly by regulating the NR4A2 gene and restoring healthy gut bacteria levels.
- The herbal formula reduced tics and abnormal movements in juvenile rat models.
- Treatment lowered neuroinflammation and oxidative stress in the striatum.
- NR4A2 silencing blocked the drug's anti-inflammatory effects in cell cultures.
- The formula restored gut microbiota balance and bile acid metabolism.
- No human clinical data or NR4A2 patient variants were evaluated.
1,25-Dihydroxyvitamin D Induces a NURR1-Tyrosine Hydroxylase Transcriptional Axis Modulated by Rexinoid/RXR Signaling in Parkinson's Disease-Relevant Human Neural Cell Models.
Sausedo MA, Mallick S, Sabir ZL, Livingston S, Nguyen QT, Doost ME, Wagner CE, Marshall PA, Haussler CA, Haussler MR, Jurutka PW
This study shows that vitamin D and retinoid compounds increase the expression of NURR1 and tyrosine hydroxylase in human cell lines, suggesting a potential pathway to support dopamine production. The findings identify a molecular mechanism where these nutrients regulate key genes involved in dopaminergic neuron function.
- Vitamin D increases NURR1 and tyrosine hydroxylase mRNA in human neuroblastoma cells.
- Retinoid compounds also boost NURR1 and tyrosine hydroxylase expression in glioblastoma cells.
- The study maps specific DNA sites where vitamin D and NURR1 regulate these genes.
- Results suggest a transcriptional axis linking vitamin D to dopamine-related gene programs.
Single-cell atlas of photoaged skin reveals JAK-STAT blockade as a strategy to reverse dermal remodeling.
Zhang M, Liu Y, Yang C, Wang C, Zou Y, Luo K, Li H, Yang R
Topical JAK inhibition reverses skin damage caused by chronic UV exposure in mice by restoring healthy cell behavior and structural integrity. This treatment normalizes stress-response pathways, including those involving the NR4A2 gene, suggesting a potential mechanism for repairing tissue remodeling.
- JAK1/2 inhibition restores collagen and elastic fiber architecture in photoaged skin.
- Treatment rebalances fibroblast trajectories away from senescence and stress states.
- The therapy normalizes NR4A2 expression among other stress-metabolic axes.
- Transitional fibroblasts drive UV-induced dermal remodeling and are key therapeutic targets.
Molecular links between reelin downregulation, topoisomerase IIβ alterations, and proteins involved in Alzheimer pathology in human SH-SY5Y neuroblastoma cell line.
Terzioglu-Usak S, Zaim M, Beker M, Isik S, Elibol B
Silencing the reelin gene in human neuroblastoma cells reduces Nurr1 protein levels and alters markers associated with Alzheimer's disease pathology. This study demonstrates a molecular link between reelin signaling and Nurr1 expression in a cell culture model.
- Reelin downregulation decreases Nurr1 protein levels in SH-SY5Y neuroblastoma cells.
- Tau and APP expressions increase when reelin is silenced in these cells.
- Topoisomerase IIβ, Psen1, and BACE1 expressions decrease with reelin loss.
- The study uses human cell lines to model molecular interactions.
- No animal models or clinical data are included in this research.
The kisspeptin analog C6 elicits greater tachyphylaxis and transcriptional activation than kisspeptin-10 and -54.
Robert V, Lomet D, Dardente H, Aucagne V, Beltramo M
The study compares three kisspeptin-based drugs and finds that the synthetic drug C6 causes stronger and longer-lasting cellular responses than the natural forms, but also leads to faster desensitization and increased activation of genes involved in inflammation and stress, which could affect its safety and effectiveness as a treatment.
- C6 causes stronger and longer-lasting cellular signaling than natural kisspeptin forms.
- C6 leads to faster desensitization (tachyphylaxis) due to greater depletion of calcium stores.
- C6 strongly activates genes involved in inflammation and stress, including NR4A2.
- These differences may impact how effective and safe each drug is in clinical use.
Genetic and epigenetic complexity of Parkinson's disease: From dopamine pathways to estrogen interplay.
Deena K, Nathish L, Fenwick EA, Karthi M, Sivasamy R
This review chapter outlines the genetic and epigenetic mechanisms underlying Parkinson's disease, noting that NR4A2 is one of several loci subject to epigenetic dysregulation. It discusses how factors like estrogen signaling and inflammation interact with dopamine pathways but does not provide specific clinical data or treatment insights for NR4A2-related syndromes.
- NR4A2 is listed as a locus affected by altered DNA methylation in Parkinson's disease.
- The text covers broad genetic factors like SNCA and LRRK2 alongside epigenetic changes.
- Estrogen signaling may offer neuroprotection through dopamine biosynthesis and antioxidant effects.
- No specific clinical evidence or treatment protocols for NR4A2 variants are presented.
Nurr1 deficiency orchestrates a coupled liver-gut pathological axis revealed by multi-omics and deep-learning histopathology.
Faisal S, Ullah I, Kambey PA, Malik A, Ejaz MA, Shah SA, Li YX
This study uses mouse models and AI to show that reduced Nurr1 causes severe liver and gut damage, identifying specific gene changes that also appear in human liver disease. It does not address the neurological symptoms or development of children with NR4A2 syndrome.
- Nurr1 deficiency causes lethal liver necrosis and gut barrier failure in mice.
- AI tools accurately classify tissue damage from standard pathology slides.
- Specific inflammatory genes upregulated in mice also rise in human liver disease.
- The research focuses on metabolic organ health, not brain development.
Comparative analysis of gene expression in mammalian claustrum subdivisions.
Fang C, Li M, Li L, Liang F, Huang J, Lu L, Lu Z, Wang H, Naumann RK
This study maps the anatomical subdivisions of the claustrum, a brain region involved in cognition and mood, by comparing gene expression patterns across various mammalian species. It identifies conserved genetic markers, including Nurr1 (NR4A2), to define structural boundaries in the brain.
- The research focuses on the claustrum's role in cortical connectivity and brain state regulation.
- Scientists compare gene expression in rats, shrews, and monkeys to map brain subdivisions.
- Nurr1 serves as one of several markers used to define these anatomical regions.
- The work establishes a comparative framework for understanding claustrum structure across species.
Isoginkgetin stabilizes atherosclerotic plaques by targeting NR4A2 to modulate the PPAR signaling pathway and reprogram ceramide metabolism, thereby inhibiting vascular smooth muscle cell phenotypic transformation.
Wei D, Zhong Z, Li H, Qi J, Liu Y, Cao H, Ma Y, Li Z, Yang G, Jiang Y, Zhang Z
This study investigates how a plant compound stabilizes heart artery plaques in mice by targeting NR4A2 to regulate lipid metabolism. It provides no information on human health, neurodevelopment, or treatments for NR4A2-related syndromes.
- Research focuses on cardiovascular disease and vascular smooth muscle cells, not the nervous system.
- The study uses mouse models of atherosclerosis, not human patients or neurological conditions.
- NR4A2 functions here as a regulator of lipid metabolism in arteries, unrelated to its role in brain development.
- Findings do not inform clinical management, prognosis, or therapy for NR4A2 syndrome.
Transcriptomic Analysis in the Liver of Two Rabbit Lines Divergently Selected for Intramuscular Fat Content.
Valdés-Hernández J, Zubiri-Gaitán A, Martínez-Álvaro M, Blasco A, Hernández P
This study found that genes involved in lipid and energy metabolism, including NR4A2, are more active in rabbits with higher intramuscular fat, suggesting the liver plays a key role in regulating meat quality through these pathways.
- Rabbits with higher intramuscular fat had more active lipid metabolism genes in the liver.
- NR4A2 was among several genes linked to lipid and energy metabolism pathways.
- The liver-muscle communication may influence meat quality through these metabolic changes.
- Key genes like CPT1B and FABP4 were part of the PPAR signaling pathway.
Early-Life Rotenone Exposure Enhances Nigrostriatal Vulnerability and Parkinsonian Neurodegeneration in Aging Rats.
Gómez-Chavarín M, Morales-Gómez R, Padilla-Mendoza JR, Padilla P, Torres-Saldaña I, Vergara-Aragón P, Silva-Lucero MD, Galindo-Solano N
Early-life exposure to the pesticide rotenone causes lasting damage to dopamine-producing neurons and accelerates Parkinson-like symptoms in aging rats. This study demonstrates that developmental environmental toxins can permanently reprogram brain cells to be more vulnerable to neurodegeneration later in life.
- Developmental rotenone exposure causes severe, persistent motor deficits starting in early adulthood.
- Early exposure leads to greater loss of dopaminergic neurons than adult-onset exposure.
- The mechanism involves epigenetic changes and cellular senescence rather than ongoing toxin presence.
- This is a rat model study with no direct human clinical data.
Differential Expression Profiles of Orphan Nuclear Receptors (NR4A) and N-myc Downstream-Regulated Gene Family (NDRG) in Patients with Inflammatory Bowel Disease.
Fonseca-Camarillo G, Furuzawa-Carballeda J, Aguilar-León D, Barreto-Zuñiga R, Martínez-Benítez B, Yamamoto-Furusho JK
This study measures NR4A2 levels in the colon tissue of patients with inflammatory bowel disease, finding that lower NR4A2 expression correlates with higher systemic inflammation markers. The research focuses entirely on gastrointestinal pathology and does not address neurological development or movement disorders associated with NR4A2 mutations.
- NR4A2 expression is reduced in the colonic mucosa of ulcerative colitis patients.
- Lower NR4A2 levels correlate with elevated inflammatory markers like CRP.
- The study investigates gut inflammation, not neurological or developmental phenotypes.
- Findings do not inform treatment strategies for NR4A2-related neurodevelopmental disorders.
Salivary gland carcinomas with BRAF fusions - an exceedingly rare and yet poorly characterized group of tumors, with potentially targetable molecular alteration.
Laco J, Bradová M, Mauramo M, Vaněček T, Kohout A, Hájek J, Hácová M, Leivo I, Molony P, Jirásek T, Agaimy A, Skálová A
This study characterizes a rare group of salivary gland cancers driven by BRAF gene fusions, identifying potential targets for specific cancer therapies. It notes that one tumor type in this cohort expresses the NR4A2 protein (Nurr1), but the research focuses entirely on oncology rather than neurodevelopment.
- BRAF fusions are exceptionally rare alterations found in specific salivary gland tumors.
- The study analyzes four cases of these rare cancers to define their molecular profile.
- One tumor expressed NR4A2 (Nurr1) protein, linking it to this cancer subtype.
- These tumors may respond to targeted MEK or RAF inhibitor therapies.
- Comprehensive molecular testing is recommended for patients with similar salivary gland tumors.
A53T α-Synuclein Expression is Associated with Altered Dopaminergic-Like Differentiation and Reduced DNA Topoisomerase IIβ Levels in an In Vitro Model of Parkinson's Disease.
Selim A, Avşar T, Neğiş Y, Işık S
This study shows that toxic alpha-synuclein reduces levels of NR4A2 (Nurr1) and impairs neuronal development in a cell culture model of Parkinson's disease. The findings suggest a mechanism where protein aggregation disrupts the genetic pathways necessary for healthy dopamine neuron formation.
- Toxic alpha-synuclein lowers NR4A2 levels in cultured neurons.
- Neuronal differentiation and growth are impaired by the mutation.
- The study uses an in vitro cell model, not human patients or animals.
- No treatment or clinical intervention is tested in this research.
Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex.
Carter JK, Quach BC, Willis C, Minto MS, Hancock DB, Montalvo-Ortiz J, Corradin O, Logan RW, Walss-Bass C, Maher BS, PGC-SUD Epigenetics Working Group, Johnson EO
This study identifies NR4A2 as one of the genes with altered expression in the brains of individuals who died from opioid overdose, suggesting a link between this gene and opioid-related neurobiology. The research does not investigate NR4A2-related syndrome or provide any clinical guidance for affected children.
- NR4A2 shows differential expression in postmortem brain tissue from opioid overdose deaths.
- The study analyzes human prefrontal cortex data to find genes linked to opioid toxicity.
- Findings highlight pathways involving neuronal plasticity and orexin signaling.
- No direct evidence links these findings to NR4A2 syndrome or treatment options.
Multi-Target Antioxidant Potential of Tricin Against Parkinson's Disease- Linked Oxidative Stress.
Giri S, Chandra P
This study uses computer modeling and cell tests to show that tricin, a plant compound, binds to several proteins involved in Parkinson's disease, including NURR1 (NR4A2). The results suggest tricin has antioxidant properties and may protect neurons from oxidative stress in preclinical models. This work does not involve human patients or clinical trials.
- Tricin binds to NURR1 and other Parkinson's-related targets in computer simulations.
- Cell tests confirm tricin scavenges free radicals and reduces oxidative stress.
- The study is preclinical; no human data or clinical trial results are presented.
- Findings suggest potential neuroprotective effects but do not prove efficacy in people.
Therapeutic Effects of Cinnamaldehyde on Neuromuscular Function in Rat Parkinson's Model Induced by Rotenone.
Buyukakilli B, Balli E, Arslan M, Demirbag HO
Cinnamaldehyde reduces oxidative stress and improves muscle function in rats with Parkinson's-like symptoms. The treatment restores dopamine levels and protects neurons in the brain regions associated with motor control.
- Study uses rotenone-induced rats, not humans or NR4A2-specific models.
- Cinnamaldehyde improves neuromuscular function and reduces oxidative stress.
- Nurr1 is measured as a marker of dopaminergic neuron health.
- No evidence links this treatment to NR4A2-related syndromes in people.
Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.
Yu X, He Y, Kamenecka TM, Kojetin DJ
This study identifies two distinct molecular mechanisms by which NR4A receptors activate gene expression when paired with RXR. It demonstrates that while some ligands work through classical coactivator recruitment, others trigger receptor dissociation, a finding that requires diverse ligand testing to fully understand.
- NR4A-RXR activation involves both classical and non-classical ligand-dependent mechanisms.
- LBD heterodimer dissociation is a key activation pathway alongside coactivator recruitment.
- Selective agonists are essential for distinguishing between these molecular mechanisms.
- Findings apply to Nurr1 and Nur77, suggesting shared pathways in neurodegeneration.
Gestational and Lactational Atrazine Exposure Potentially Mediates Behavioral and Dopaminergic Alterations in Rat Offspring: Insights into Nurr1-Related ceRNA Regulation.
Ma Y, Sun T, Pan M, Zheng Z, Wei J, Yuan X, Wan J, Zhou Y, Sun Y
Exposure to the herbicide atrazine during pregnancy and breastfeeding causes behavioral issues and damage to dopamine-producing neurons in rat offspring. The study identifies a specific molecular pathway involving Elavl4, miR-301a-5p, and Nurr1 that mediates this neuronal injury. Restoring Elavl4 levels partially reverses the reduction of Nurr1 in cell models, suggesting a potential mechanism for neuroprotection.
- Atrazine exposure harms dopamine neurons and alters behavior in rat pups.
- The study links this damage to a specific RNA regulatory network involving Nurr1.
- Increasing Elavl4 levels partially restores Nurr1 expression in damaged cells.
- This is a preclinical animal and cell study with no human data.
Single-cell Analysis Reveals a LAMB3-dependent Immunosuppressive Environment in Gallbladder Neck/Cystic Duct Carcinoma.
Shi X, Li S, Bai M, Xie Z, Cheng Q, Qiu X, Zhou T, Jiang X, Yang S, Hu J, Xue D, Liu S, Zhang Y, Wang Y, Wu J, Bao J, Wang H, Jiang X, Chen L
Gallbladder cancer in the neck/cystic duct (GBCN/CD) creates a highly immunosuppressive environment driven by a protein called LAMB3, which helps tumor cells evade the immune system. This makes GBCN/CD resistant to current immunotherapies, but targeting LAMB3 could potentially restore immune response and improve treatment. The findings suggest that GBCN/CD needs a different treatment strategy than other gallbladder cancers.
- GBCN/CD tumors are immunosuppressive due to LAMB3 protein
- LAMB3 drives immune evasion by altering macrophages and T cells
- Targeting LAMB3 may reverse immune suppression in GBCN/CD
- GBCN/CD does not respond well to current immunotherapies
- LAMB3 is a promising new treatment target