Age-dependent decrease of Nurr1 protein expression in the gerbil hippocampus.
Ahn JH, Lee JS, Cho JH, Park JH, Lee TK, Song M, Kim H, Kang SH, Won MH, Lee CH
Nurr1 protein levels decline significantly in the hippocampus as gerbils age, correlating with reduced cognitive function. This natural aging process in a non-human model does not provide direct evidence for treating NR4A2-related syndromes in children.
- Nurr1 protein decreases gradually in the gerbil hippocampus with advancing age.
- Reduction is most severe in aged animals compared to young and adult groups.
- Declining Nurr1 levels associate with normal aging and cognitive decline in gerbils.
- Study uses animal models, offering no direct clinical guidance for human patients.
Proliferation and committed differentiation into dopamine neurons of neural stem cells induced by the active ingredients of radix astragali.
Gao H, Dou L, Shan L, Sun Y, Li W
Active ingredients from the herb radix astragali stimulate neural stem cells to multiply and differentiate into dopamine-producing neurons in a laboratory dish. This process involves increasing the expression of key genes, including Nurr1 (NR4A2), sonic hedgehog, and Ptx3, which drive the formation of these specific brain cells.
- Radix astragali extracts boost neural stem cell proliferation in vitro.
- The compounds induce differentiation into dopamine neurons specifically.
- Treatment upregulates Nurr1 (NR4A2), Shh, and Ptx3 gene expression.
- This is a preclinical study using cell cultures, not humans or animals.
DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.
Zaim M, Isik S
Overexpressing DNA topoisomerase IIβ promotes neurite growth in human stem cells by regulating Rho-GTPases and increasing Nurr1 levels. Silencing this enzyme reduces neural differentiation and alters cell morphology, suggesting a role in maintaining neuronal structure.
- Topo IIβ overexpression increases neurite length in human stem cells.
- Silencing Topo IIβ reduces neural differentiation efficiency and neurite growth.
- Nurr1 expression levels correlate directly with Topo IIβ presence.
- The mechanism involves downregulating RhoA/Rock2 and upregulating Cdc42.
Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells.
Parvin R, Noro E, Saito-Hakoda A, Shimada H, Suzuki S, Shimizu K, Miyachi H, Yokoyama A, Sugawara A
This study investigates a potential drug for Cushing's disease using mouse pituitary tumor cells, not human patients or NR4A2-related conditions. The research focuses on how the drug affects hormone production pathways unrelated to the dopaminergic system relevant to NR4A2 syndromes.
- Study uses mouse pituitary cells, not human tissue or patients.
- Focuses on Cushing's disease treatment, not NR4A2 syndrome.
- No connection to dopaminergic neurons or motor symptoms.
- Preclinical molecular biology with no clinical application for this child.
Neural Stem Cell Grafts Promote Astroglia-Driven Neurorestoration in the Aged Parkinsonian Brain via Wnt/β-Catenin Signaling.
L'Episcopo F, Tirolo C, Peruzzotti-Jametti L, Serapide MF, Testa N, Caniglia S, Balzarotti B, Pluchino S, Marchetti B
Transplanted neural stem cells restore damaged dopamine neurons in aged mice with Parkinson's disease by triggering astrocytes to activate a specific repair signaling pathway. This approach demonstrates that supporting the brain's own glial cells can reverse neuronal loss and immune dysfunction in an aging, diseased environment.
- Neural stem cell grafts convert into astrocytes that trigger neuron repair in aged Parkinsonian mice.
- The Wnt/beta-catenin signaling pathway drives the restoration of dopamine neurons and reduces inflammation.
- Blocking this signaling pathway stops the therapeutic benefits, confirming its essential role in neurorestoration.
Nurr1: A vital participant in the TLR4-NF-κB signal pathway stimulated by α-synuclein in BV-2 cells.
Shao QH, Yan WF, Zhang Z, Ma KL, Peng SY, Cao YL, Yuan YH, Chen NH
This study shows that Nurr1 reduces inflammation in immune cells by blocking a specific signaling pathway triggered by abnormal protein aggregates. The findings are based entirely on cell cultures and mouse models, with no human data or direct clinical application established.
- Nurr1 inhibits inflammatory responses in microglia by interacting with NF-κB.
- The research uses only BV-2 cells and mouse models, not human subjects.
- No evidence exists yet for treating NR4A2-related syndromes or Parkinson's in people.
- This is basic molecular biology explaining a mechanism, not a therapy test.
Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance.
Hibino S, Chikuma S, Kondo T, Ito M, Nakatsukasa H, Omata-Mise S, Yoshimura A
Blocking NR4A proteins in regulatory T cells removes their ability to suppress immune responses, allowing the body's own immune system to attack tumors more effectively. This approach boosts anti-tumor immunity without causing major autoimmune side effects in mice.
- NR4A proteins help regulatory T cells suppress immune attacks on tumors
- Turning off NR4A in T cells helps immune cells fight cancer
- Existing drugs can block NR4A activity and enhance anti-tumor responses
- This strategy works without causing severe autoimmunity in models
- Could lead to new cancer treatments targeting immune suppression
miR-381-3p knockdown improves intestinal epithelial proliferation and barrier function after intestinal ischemia/reperfusion injury by targeting nurr1.
Liu L, Yao J, Li Z, Zu G, Feng D, Li Y, Qasim W, Zhang S, Li T, Zeng H, Tian X
Inhibiting a specific microRNA restores intestinal barrier function and improves survival in mice suffering from ischemia/reperfusion injury by increasing the activity of Nurr1. This study demonstrates that Nurr1 is essential for protecting gut tissue during acute physical stress, but it does not address neurodevelopmental outcomes or motor symptoms relevant to NR4A2 syndrome.
- Nurr1 supports intestinal epithelial proliferation and barrier integrity after injury.
- Blocking miR-381-3p boosts Nurr1 levels and reduces tissue damage in mice.
- The protective effect relies entirely on Nurr1-mediated pathways.
- This research focuses on acute gut injury, not neurological development.
- No clinical data or human trials are included in this study.
Generation of Dopamine-Secreting Cells from Human Adipose Tissue-Derived Stem Cells In Vitro.
Soheilifar MH, Javeri A, Amini H, Taha MF
Researchers successfully converted human fat-derived stem cells into dopamine-secreting neurons in a lab dish using specific growth factors. These engineered cells express key dopaminergic markers and release dopamine when stimulated, demonstrating the potential for cell replacement therapies.
- Human adipose stem cells differentiate into dopamine-secreting neurons in vitro.
- A specific growth factor cocktail drives this dopaminergic specification.
- Differentiated cells express TH, NURR1, and other dopaminergic markers.
- Cells release significant dopamine upon electrical stimulation.
- This approach offers a potential source for Parkinson's disease cell therapy.
Correlation between Nurr1 expression and drug resistance in the brain of rats with epilepsy.
Li HY, Liu F, Wang HR
This study finds that Nurr1 levels rise in the brains of rats with drug-resistant epilepsy and correlate with markers of drug resistance. The findings are based entirely on animal models and do not provide evidence for human treatment or NR4A2-related syndromes.
- Nurr1 protein increases in rat hippocampus during drug-resistant epilepsy.
- Higher Nurr1 correlates with increased drug-resistance markers in rats.
- The study uses only rat models, not human patients.
- No clinical relevance for NR4A2 syndrome or human therapy is established.
Effects of rhynchophylline on the hippocampal miRNA expression profile in ketamine-addicted rats.
Li C, Tu G, Luo C, Guo Y, Fang M, Zhu C, Li H, Ou J, Zhou Y, Liu W, Yung KKL, Mo Z
This study examines how a compound called rhynchophylline affects gene regulation in the brains of rats addicted to ketamine. It identifies a specific molecular pathway involving miR-331-5p and Nurr1 that changes during addiction and is modified by the treatment.
- The study uses rat models of ketamine addiction, not human patients.
- Rhynchophylline alters miRNA expression in the hippocampus of addicted rats.
- miR-331-5p negatively regulates Nurr1 protein levels in this context.
- Nurr1 is a transcription factor, but this paper focuses on addiction mechanisms.
- No clinical data or direct relevance to NR4A2-related developmental syndromes is presented.
Rhynchophylline Downregulates Phosphorylated cAMP Response Element Binding Protein, Nuclear Receptor-related-1, and Brain-derived Neurotrophic Factor Expression in the Hippocampus of Ketamine-induced Conditioned Place Preference Rats.
Guo Y, Luo C, Tu G, Li C, Liu Y, Liu W, Lam Yung KK, Mo Z
Rhynchophylline, a plant-derived alkaloid, reverses ketamine-induced behavioral changes in rats by normalizing hippocampal levels of Nurr1, p-CREB, and BDNF. This preclinical study suggests that modulating these specific proteins may mitigate drug reward pathways.
- Rhynchophylline reduces ketamine-seeking behavior in a rat model of addiction.
- The treatment restores hippocampal Nurr1 levels altered by ketamine exposure.
- Nurr1, p-CREB, and BDNF are key molecular targets in this mechanism.
- Findings are limited to animal models with no human clinical data.
NR4A2 protects cardiomyocytes against myocardial infarction injury by promoting autophagy.
Liu H, Liu P, Shi X, Yin D, Zhao J
NR4A2 helps protect heart cells after a heart attack by boosting autophagy, a process that clears out damaged components. Lower NR4A2 levels increase cell death, while increasing NR4A2 reduces damage, suggesting it could be a target for treating heart failure.
- NR4A2 protects heart cells after a heart attack
- NR4A2 boosts autophagy to reduce cell death
- Low NR4A2 leads to more heart damage
- NR4A2 blocks p53/Bax, a key cell death pathway
- miR-212-3p reduces NR4A2 levels
Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells.
Miyai T, Takano J, Endo TA, Kawakami E, Agata Y, Motomura Y, Kubo M, Kashima Y, Suzuki Y, Kawamoto H, Ikawa T
This study identifies Nr4a2 as a critical early factor required for the development of B cells in the immune system. It demonstrates that Nr4a2 acts in a three-step process to prime multipotent progenitor cells before they commit to becoming B lymphocytes.
- Nr4a2 is an immediate early gene essential for B-cell lineage commitment.
- Inhibiting Nr4a2 severely impairs the generation of B cells in vitro.
- The research maps a three-step transcriptional circuit driving immune cell development.
- Findings provide a blueprint for understanding normal and cancerous B-lymphocyte growth.
Conserved Upstream Regulatory Regions in Mammalian Tyrosine Hydroxylase.
Wang M, Fones L, Cave JW
This study identifies five conserved DNA regions upstream of the Tyrosine Hydroxylase gene that help control its expression in catecholamine-producing neurons. It confirms that NURR1 (NR4A2) and other transcription factors bind to these regions, while also discovering a new regulatory role for the CTCF protein in the forebrain.
- Five conserved DNA regions upstream of the Tyrosine Hydroxylase gene regulate its expression.
- NURR1 binds to these conserved regions to help control neuron-specific gene activity.
- CTCF is identified as a novel regulator of Tyrosine Hydroxylase transcription in the forebrain.
- The research maps the genomic architecture controlling key enzymes in dopamine production.
Bioactive Dietary VDR Ligands Regulate Genes Encoding Biomarkers of Skin Repair That Are Associated with Risk for Psoriasis.
Karrys A, Rady I, Chamcheu RN, Sabir MS, Mallick S, Chamcheu JC, Jurutka PW, Haussler MR, Whitfield GK
This study investigates how dietary compounds DHA and curcumin influence skin repair genes in human keratinocytes, noting that they modulate the transcription factor NR4A2/NURR1. The research focuses on psoriasis mechanisms and does not provide evidence regarding NR4A2-related syndromes or their treatment.
- DHA and curcumin activate skin repair genes in human keratinocytes with specific genetic deletions.
- These compounds reduce inflammation markers by opposing TNF-alpha signaling pathways.
- NR4A2/NURR1 is identified as a transcription factor modulated by these dietary ligands.
- The findings relate to psoriasis treatment mechanisms, not NR4A2 syndrome pathology.
Identification of key microRNAs, transcription factors and genes associated with congenital obstructive nephropathy in a mouse model of megabladder.
Xin G, Chen R, Zhang X
This study identifies specific microRNAs and transcription factors, including NR4A2, that regulate gene networks in a mouse model of congenital kidney obstruction. The findings highlight molecular pathways involving Vegfa, Pten, and Kras that may contribute to the development of this condition.
- Researchers analyzed kidney tissue from mice with megabladder to find molecular causes of obstruction.
- Three key microRNAs were identified as regulators in the affected kidney tissue.
- NR4A2 is part of a regulatory network targeting Vegfa in this mouse model.
- The study focuses on congenital obstructive nephropathy, not NR4A2-related neurological syndromes.
- Results are based on preclinical animal data with no human clinical application.
Regulatory effects of Nr4a2 on Th2 cells from patients with pemphigus vulgaris.
Chen J, Zhang Y, Liang Y, Zhao M, Long H, Xiao R, Wu H, Liao J, Luo S, Zhang G, Lu Q
In people with pemphigus vulgaris, a rare autoimmune skin disease, levels of the NR4A2 protein in immune cells are lower than normal, and this drop is linked to increased activity of Th2 cells and harmful immune signals. Boosting NR4A2 reduces these harmful immune responses, suggesting it helps control the disease.
- NR4A2 levels are low in immune cells of pemphigus patients
- Low NR4A2 links to overactive Th2 immune cells
- Increasing NR4A2 reduces harmful immune signals
- NR4A2 may help control autoimmune skin disease
microRNA-137 promotes endothelial progenitor cell proliferation and angiogenesis in cerebral ischemic stroke mice by targeting NR4A2 through the Notch pathway.
Liu XL, Wang G, Song W, Yang WX, Hua J, Lyu L
This study shows that miR-137 promotes blood vessel growth in mouse brains after stroke by suppressing the NR4A2 gene. It establishes a molecular link between NR4A2, the Notch pathway, and endothelial cell survival in an ischemic model.
- NR4A2 levels are elevated in mouse brain tissue following cerebral ischemic stroke.
- miR-137 suppresses NR4A2 to enhance endothelial progenitor cell proliferation.
- The mechanism involves modulation of the Notch signaling pathway components.
- Restoring miR-137 or silencing NR4A2 reduces apoptosis in damaged cells.
Pink1 Regulates Tyrosine Hydroxylase Expression and Dopamine Synthesis.
Lu L, Jia H, Gao G, Duan C, Ren J, Li Y, Yang H
This study identifies a molecular pathway where the PINK1 protein regulates dopamine production by controlling the activity of Nurr1, the transcription factor encoded by NR4A2. While it confirms that Nurr1 is essential for synthesizing tyrosine hydroxylase, the findings are derived from cell cultures and do not provide direct evidence for treating NR4A2-related syndromes in humans.
- PINK1 deficiency reduces dopamine by suppressing tyrosine hydroxylase expression.
- Nurr1 (NR4A2) activity is required for normal tyrosine hydroxylase levels.
- Research relies on dopaminergic cell lines, not human patients or animal models.
- No clinical data or treatment implications for NR4A2 syndrome are presented.
CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters.
Parra-Damas A, Rubió-Ferrarons L, Shen J, Saura CA
Neuronal activity triggers the recruitment of the coactivator CRTC1 to specific gene promoters, including NR4A2, to drive their expression. This mechanism explains how brain signals selectively activate NR4A2 and related genes through a physical interaction with CREB at TATA-containing promoter regions.
- CRTC1 binds to NR4A2 promoters only when neurons are active.
- CREB stays bound to NR4A2 DNA regardless of neuronal activity.
- Activity causes CRTC1 to move into the nucleus and join CREB.
- This complex formation initiates transcription of NR4A2 and similar genes.
Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation.
Ji H, Xu L, Wang Z, Fan X, Wu L
Glyphosate exposure during pregnancy and lactation alters microRNA expression in the developing mouse brain, specifically downregulating Nr4a2. These changes disrupt Wnt and Notch signaling pathways critical for normal neural development.
- Glyphosate exposure reduces Nr4a2 levels in the prefrontal cortex of mouse offspring.
- The study identifies disruptions in Wnt and Notch signaling pathways.
- These findings link environmental toxins to potential neurodevelopmental mechanisms.
- Research relies entirely on animal models, not human data.
Liver X receptors agonist promotes differentiation of rat bone marrow derived mesenchymal stem cells into dopaminergic neuron-like cells.
Cheng O, Tian X, Luo Y, Mai S, Yang Y, Kuang S, Chen Q, Ma J, Chen B, Li R, Yang L, Li H, Hu C, Zhang J, Chen Z, Li Y, Xia H, Xu Y, Yang J
This study shows that activating liver X receptors in rat stem cells increases the efficiency of converting them into dopamine-producing neuron-like cells. The findings suggest this pathway could help optimize cell replacement therapies for Parkinson's disease.
- LXR agonists boost the conversion rate of rat stem cells into dopamine neurons.
- The treatment shortens the time required for cellular differentiation in vitro.
- Results rely on rat models, not human clinical data.
- This research focuses on Parkinson's disease mechanisms, not NR4A2 syndrome.
A screening system to identify transcription factors that induce binding site-directed DNA demethylation.
Suzuki T, Maeda S, Furuhata E, Shimizu Y, Nishimura H, Kishima M, Suzuki H
This study establishes a screening method to identify transcription factors that cause site-specific DNA demethylation and confirms that NR4A2 performs this function in cell models. The research demonstrates that NR4A2 actively removes methyl groups from specific genomic regions associated with its biological roles, such as cellular differentiation.
- Researchers developed a new screening system to find transcription factors that direct DNA demethylation.
- The study identifies eight novel transcription factors, including NR4A2, that induce binding site-directed demethylation.
- NR4A2 targets highly methylated CpG sites for local demethylation in model cells.
- Demethylated regions identified by NR4A2 overlap with those of other family members.
- The findings describe the molecular mechanism of NR4A2 but do not test treatments or human outcomes.
miR-145-5p/Nurr1/TNF-α Signaling-Induced Microglia Activation Regulates Neuron Injury of Acute Cerebral Ischemic/Reperfusion in Rats.
Xie X, Peng L, Zhu J, Zhou Y, Li L, Chen Y, Yu S, Zhao Y
This rat study shows that blocking a specific microRNA (miR-145-5p) increases Nurr1 levels in brain immune cells, which reduces inflammation and protects neurons from stroke damage. The treatment improved neurological outcomes in the animal model by interrupting a harmful signaling pathway involving TNF-α.
- Blocking miR-145-5p raises Nurr1 levels in rat microglia during acute brain injury.
- Higher Nurr1 suppresses inflammatory TNF-α, reducing neuron death after stroke.
- Treatment decreased infarct size and improved neurological function in rats.
- This is preclinical animal research with no human clinical data.
Long 3'UTR of Nurr1 mRNAs is targeted by miRNAs in mesencephalic dopamine neurons.
Pereira LA, Munita R, González MP, Andrés ME
This study identifies specific microRNAs that regulate the levels of Nurr1 protein in rat dopamine neurons by targeting a long variant of its mRNA. The findings demonstrate a mechanism for fine-tuning Nurr1 expression, which is critical for neuron survival and development.
- Researchers identified a long 3'UTR variant of rat Nurr1 mRNA.
- MicroRNAs miR-93, miR-204, and miR-302d target this specific variant.
- These microRNAs significantly reduce Nurr1 protein levels in neurons.
- The study uses rat models and cell culture techniques.
- No human data or clinical treatment implications are presented.
Tcf12 Is Involved in Early Cell-Fate Determination and Subset Specification of Midbrain Dopamine Neurons.
Mesman S, Smidt MP
This study identifies Tcf12 as a critical regulator for the early development and subset specification of midbrain dopamine neurons in mice. Loss of Tcf12 during early embryonic stages disrupts the spatial expression of key developmental markers like Nurr1 and leads to a significant reduction in dopamine-producing neurons.
- Tcf12 regulates early cell-fate commitment of neural progenitors in the midbrain.
- Early loss of Tcf12 reduces rostral tyrosine hydroxylase expression in mice.
- Tcf12 also influences late-stage subset specification of dopamine neurons.
- The study uses mouse embryos to map these developmental mechanisms.
A Bioinformatic Algorithm for Analyzing Cell Signaling Using Temporal Proteomic Data.
Zhang C, Chen Y, Mao X, Huang Y, Jung SY, Jain A, Qin J, Wang Y
This paper presents a statistical algorithm for analyzing proteomic data, using HeLa cells to identify transcription factors influenced by the drug gefitinib. NR4A2 appears only as one of several known responders in this cancer cell line study, with no focus on neurological function or human patients.
- The study uses a bioinformatic algorithm to analyze temporal proteomic data from HeLa cells.
- NR4A2 is identified as a known responder to EGF signaling in these cancer cells.
- Research focuses on gefitinib targets and ErbB pathway inhibition in oncology.
- No human clinical data, animal models of NR4A2 syndrome, or dopaminergic mechanisms are included.