Compensatory Expression of Nur77 and Nurr1 Regulates NF-κB-Dependent Inflammatory Signaling in Astrocytes.
Popichak KA, Hammond SL, Moreno JA, Afzali MF, Backos DS, Slayden RD, Safe S, Tjalkens RB
Activating the NR4A2/Nurr1 and NR4A1/Nur77 proteins with a drug called C-DIM5 reduces harmful inflammation in brain cells called astrocytes, which may protect dopamine-producing neurons. This effect happens inside the cell nucleus and depends on both Nurr1 and Nur77 working together to block inflammatory signals.
- C-DIM5 boosts Nurr1 and Nur77 levels in brain cells
- This reduces inflammation linked to Parkinson’s disease
- The drug works inside the nucleus, not by blocking NF-κB entry
- Both Nurr1 and Nur77 are needed for the anti-inflammatory effect
- Suggests a potential treatment strategy for NR4A2-related conditions
Medial habenula maturational deficits associate with low motivation for voluntary physical activity.
Grigsby KB, Kelty TJ, Booth FW
Rats bred to run more show better development and maturity in the medial habenula, a brain region linked to motivation, suggesting this area helps drive physical activity. Differences in gene expression, neuron maturation, and brain structure in this region correlate with how much rats voluntarily run.
- Higher medial habenula maturity links to greater voluntary running
- Key genes like Nurr1 and Brn3a are more active in high-run rats
- Neuron and dendrite development are more advanced in active rats
- Immature brain structures are more common in low-run rats
- Medial habenula may be a target for boosting motivation to move
NR4A2 haploinsufficiency is associated with intellectual disability and autism spectrum disorder.
Lévy J, Grotto S, Mignot C, Maruani A, Delahaye-Duriez A, Benzacken B, Keren B, Haye D, Xavier J, Heulin M, Charles E, Verloes A, Dupont C, Pipiras E, Tabet AC
NR4A2 gene loss is strongly linked to neurodevelopmental issues like intellectual disability and autism, with symptoms appearing in all reported cases. The condition results from having only one working copy of the gene, which is likely enough to cause significant developmental problems.
- NR4A2 gene loss causes intellectual disability and autism
- Only one functional copy of NR4A2 is insufficient for normal development
- Symptoms include language delay and developmental issues
- Deletions affecting only NR4A2 are sufficient to cause disease
- This condition has high penetrance in affected individuals
Abrogation of the Circadian Nuclear Receptor REV-ERBα Exacerbates 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration.
Kim J, Jang S, Choi M, Chung S, Choe Y, Choe HK, Son GH, Rhee K, Kim K
Reducing REV-ERBα worsens dopamine neuron damage and motor problems in a mouse model of Parkinson’s disease, suggesting that REV-ERBα normally protects these neurons. This protection may involve calming brain inflammation and supporting the function of NURR1, a key protein linked to NR4A2-related disorders.
- REV-ERBα loss increases vulnerability of dopamine neurons to damage
- Lack of REV-ERBα worsens motor symptoms and neuron loss
- Exaggerated brain inflammation likely drives the damage
- REV-ERBα works with NURR1 to support dopamine neuron health
- Targeting REV-ERBα may help protect neurons in NR4A2-related conditions
HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage.
Loppi S, Kolosowska N, Kärkkäinen O, Korhonen P, Huuskonen M, Grubman A, Dhungana H, Wojciechowski S, Pomeshchik Y, Giordano M, Kagechika H, White A, Auriola S, Koistinaho J, Landreth G, Hanhineva K, Kanninen K, Malm T
HX600, a drug that activates the Nurr1 protein, reduces brain inflammation and protects neurons in models of stroke. It helps prevent brain damage and improves movement recovery in mice after stroke by calming harmful immune responses in the brain.
- HX600 activates Nurr1, reducing brain inflammation
- Protects neurons and improves movement after stroke in mice
- Reduces harmful immune cell activity and brain damage
- Lowers levels of inflammatory brain metabolites
- Offers a potential new treatment for stroke-related brain injury
Maternal Vitamin D Prevents Abnormal Dopaminergic Development and Function in a Mouse Model of Prenatal Immune Activation.
Luan W, Hammond LA, Vuillermot S, Meyer U, Eyles DW
Maternal vitamin D supplementation during pregnancy can prevent abnormal dopamine system development and function in mouse offspring exposed to prenatal immune activation, a model linked to schizophrenia. It helps protect fetal dopamine neurons and restores their proper positioning and gene expression.
- Vitamin D during pregnancy protects dopamine neurons in offspring
- Prevents abnormal dopamine responses linked to schizophrenia
- Restores normal gene expression and neuron positioning
- May help prevent neurodevelopmental issues from prenatal immune activation
- Cholecalciferol (dietary vitamin D) could be a preventive strategy
A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration.
Yang S, Toledo EM, Rosmaninho P, Peng C, Uhlén P, Castro DS, Arenas E
Zeb2 and miR-200c work together to control the timing of midbrain dopamine neuron development by keeping progenitor cells from maturing too early. Disrupting this balance leads to problems in neuron formation and movement, which are critical for brain function.
- Zeb2 and miR-200c regulate dopamine neuron development
- Imbalance causes premature maturation and migration defects
- Zeb2 controls key genes like NR4A2 and PITX3
- This pathway maintains proper timing of neuron formation
- Findings may inform therapies for dopamine-related disorders
The lentiviral-mediated Nurr1 genetic engineering mesenchymal stem cells protect dopaminergic neurons in a rat model of Parkinson's disease.
Wang X, Zhuang W, Fu W, Wang X, Lv E, Li F, Zhou S, Rausch WD, Wang X
Engineered stem cells that produce the Nurr1 protein protect dopamine-producing brain cells and improve movement in a rat model of Parkinson's disease, suggesting a potential therapy for NR4A2-related disorders.
- Nurr1-engineered stem cells survive and migrate in the brain
- They reduce brain inflammation and protect dopamine neurons
- Improved movement and neuron counts were seen in Parkinson's rats
- This approach may help treat NR4A2-related neurological conditions
Generation of dopamine neuronal-like cells from induced neural precursors derived from adult human cells by non-viral expression of lineage factors.
Playne R, Jones K, Connor B
This study shows that adult human cells can be directly reprogrammed into neural precursors that develop into dopamine neuron-like cells, offering a potential way to model Parkinson's disease using patient-derived cells, though the cells do not fully mature into authentic midbrain dopamine neurons.
- Adult human cells can be turned into dopamine neuron-like cells without going through stem cells
- The resulting cells express key dopamine markers but lack early midbrain identity markers
- Current methods don't yet produce fully authentic midbrain dopamine neurons
- This approach may help model Parkinson's disease using aged or patient-specific cells
- Direct reprogramming could support future drug testing and disease research
Endogenous Purification of NR4A2 (Nurr1) Identified Poly(ADP-Ribose) Polymerase 1 as a Prime Coregulator in Human Adrenocortical H295R Cells.
Noro E, Yokoyama A, Kobayashi M, Shimada H, Suzuki S, Hosokawa M, Takehara T, Parvin R, Shima H, Igarashi K, Sugawara A
PARP1 is a key protein that works with NR4A2 (Nurr1) to control aldosterone production in human adrenal cells. Blocking PARP1 reduces the activity of genes involved in hormone production and lowers aldosterone release in response to stress signals.
- PARP1 directly interacts with NR4A2 (Nurr1) in human adrenal cells
- PARP1 is essential for NR4A2 to activate genes needed for aldosterone production
- Inhibiting PARP1 reduces aldosterone secretion in response to angiotensin II
- PARP1 inhibitors may offer a new way to modulate hormone levels in NR4A2-related conditions
Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin II.
Takeda Y, Demura M, Wang F, Karashima S, Yoneda T, Kometani M, Hashimoto A, Aono D, Horike SI, Meguro-Horike M, Yamagishi M, Takeda Y
Changes in DNA methylation can turn on the aldosterone synthase gene (CYP11B2), which is involved in hormone production, and this process is influenced by salt levels and blood pressure signals. This gene's activity is regulated by transcription factors like NURR1 (NR4A2), whose ability to bind DNA is reduced when the gene is methylated.
- DNA hypomethylation activates the CYP11B2 gene
- NR4A2 (NURR1) binding is blocked by DNA methylation
- Low salt and angiotensin II increase CYP11B2 expression
- Methylation changes are reversible and responsive to physiological signals
- MECP2 protein binds methylated CYP11B2 promoter
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 in the hippocampus decline steadily with age in gerbils, which may contribute to age-related cognitive decline. This suggests that maintaining Nurr1 function could be important for brain health as we age.
- Nurr1 levels drop in the hippocampus as gerbils age
- Low Nurr1 is linked to reduced cognitive function
- Pyramidal and granule neurons show the most Nurr1 loss
- This decline may mirror human brain aging
- Supports Nurr1 as a potential target for brain health
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
The active ingredients in astragalus root can boost the growth of neural stem cells and guide them to become dopamine-producing neurons in lab tests. This effect may happen by increasing levels of key genes involved in dopamine neuron development, including Nurr1.
- Astragalus ingredients boost neural stem cell growth
- They help turn stem cells into dopamine neurons
- Effect may involve boosting Nurr1 and related genes
- Findings are from lab studies, not human trials
- Potential relevance to Parkinson’s disease therapies
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
Topo IIβ helps control nerve growth in human stem cells by balancing key proteins involved in cell shape and movement, including Nurr1, which is linked to NR4A2-related syndrome. When Topo IIβ is missing, nerve growth is impaired and harmful changes occur in Rho-GTPase pathways. Boosting Topo IIβ improves nerve growth and corrects these imbalances.
- Topo IIβ supports nerve growth in human stem cells
- Low Topo IIβ disrupts Rho-GTPase balance and nerve development
- Topo IIβ boosts Nurr1, the protein affected in NR4A2 syndrome
- Restoring Topo IIβ improves nerve cell structure and function
- This suggests a potential pathway for future treatments
Environmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression.
Wassouf Z, Hentrich T, Samer S, Rotermund C, Kahle PJ, Ehrlich I, Riess O, Casadei N, Schulze-Hentrich JM
An enriched environment prevents many of the harmful gene changes caused by alpha-synuclein overexpression in mice, including disruptions in synaptic function and reduced levels of key genes like NURR1. This protective effect is linked to sustained activation of immediate early genes, including Nr4a2/Nurr1, which may help maintain brain health despite disease-related stress.
- Enriched environments block gene disruptions from alpha-synuclein overexpression
- NURR1 and other immediate early genes stay active in enriched settings
- This suggests a natural protective pathway that could inspire new treatments
- The findings highlight environmental factors as powerful modulators of brain gene activity
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
MEKT1, a new PPAR-γ agonist, strongly reduces ACTH production in cells that mimic Cushing's disease by blocking the activity of key genes and proteins involved in hormone overproduction, including NR4A2 (Nurr1) and its binding sites.
- MEKT1 reduces ACTH secretion in Cushing's disease model cells
- MEKT1 blocks NR4A2 (Nurr1) and its target gene activity
- MEKT1 disrupts protein binding to DNA regions critical for hormone production
- MEKT1 outperforms rosiglitazone and pioglitazone in suppressing hormone genes
- Findings suggest MEKT1 could be a promising treatment for Cushing's disease
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 help restore dopamine-producing brain cells in aged mice with Parkinson's-like disease by turning into supportive astrocytes that activate a key repair pathway. This process boosts neuron survival and reduces harmful brain inflammation, offering a potential therapy for aging-related Parkinson's.
- Neural stem cells become supportive astrocytes in the brain
- They trigger a repair pathway (Wnt/β-catenin) that saves dopamine neurons
- This reduces brain inflammation and restores neuron function
- Blocking the repair pathway stops the benefits
- Suggests a promising treatment for aged Parkinson's brains
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
Nurr1 reduces brain inflammation caused by abnormal alpha-synuclein, a protein linked to Parkinson’s disease, by blocking a key inflammatory pathway. This suggests boosting Nurr1 could protect brain cells and may lead to new treatments for Parkinson’s and related disorders.
- Nurr1 reduces harmful brain inflammation from alpha-synuclein
- Alpha-synuclein triggers inflammation via TLR4 and NF-κB
- Nurr1 blocks NF-κB from entering the nucleus to stop inflammation
- Boosting Nurr1 may protect brain cells in Parkinson’s disease
- This pathway offers a potential target for new therapies
The Nurr1 Ligand,1,1-bis(3'-Indolyl)-1-(p-Chlorophenyl)Methane, Modulates Glial Reactivity and Is Neuroprotective in MPTP-Induced Parkinsonism.
Hammond SL, Popichak KA, Li X, Hunt LG, Richman EH, Damale PU, Chong EKP, Backos DS, Safe S, Tjalkens RB
A compound called C-DIM12 activates the Nurr1 protein, which helps reduce brain inflammation and protects dopamine-producing neurons in a mouse model of Parkinson's disease. This suggests that targeting Nurr1 could be a promising strategy to slow or prevent neurodegeneration in conditions like NR4A2-related syndrome.
- C-DIM12 activates Nurr1, a key protein linked to NR4A2-related disorders
- It reduces harmful brain inflammation and protects dopamine neurons
- The drug reaches high levels in the brain, making it effective in animal models
- Nurr1 activation may slow neurodegeneration in Parkinson’s and similar conditions
Ultrasound-Triggered Effects of the Microbubbles Coupled to GDNF Plasmid-Loaded PEGylated Liposomes in a Rat Model of Parkinson's Disease.
Yue P, Miao W, Gao L, Zhao X, Teng J
Delivering a gene that makes GDNF, a brain-protective protein, using ultrasound and special nanoparticles improves movement and protects brain cells in a rat model of Parkinson's disease. This approach also boosts levels of Nurr1, a key protein involved in dopamine neuron health.
- Ultrasound helps deliver GDNF gene to the brain
- GDNF and Nurr1 levels increase after treatment
- Movement problems and neuron loss are reduced
- Nanoparticles improve gene delivery safety
- Potential therapy for Parkinson's disease
Kir6.2 Deficiency Promotes Mesencephalic Neural Precursor Cell Differentiation via Regulating miR-133b/GDNF in a Parkinson's Disease Mouse Model.
Zhou Y, Zhu J, Lv Y, Song C, Ding J, Xiao M, Lu M, Hu G
Reducing Kir6.2 activity boosts the brain's natural repair process by increasing the formation of dopamine-producing neurons from precursor cells in a Parkinson's disease mouse model. This happens through a pathway involving microRNA-133b and the growth factor GDNF, which supports neuron survival and development.
- Kir6.2 deficiency enhances dopamine neuron regeneration
- It works by boosting GDNF and reducing miR-133b
- This reveals a new target for protecting brain cells in Parkinson’s
- The effect occurs through endogenous neural precursor cells
- Findings suggest potential for new Parkinson’s treatments
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
Blocking miR-381-3p helps repair the gut lining after injury by boosting NURR1, a protein important for gut cell growth and barrier function. This improves survival and reduces damage to other organs in mouse models.
- miR-381-3p blocks NURR1, harming gut repair after injury
- Reducing miR-381-3p boosts gut cell growth and barrier function
- NURR1 is essential for the protective effect of miR-381-3p inhibition
- This approach improves survival and reduces organ damage
- Potential for new treatments targeting this pathway
Generation of Dopamine-Secreting Cells from Human Adipose Tissue-Derived Stem Cells In Vitro.
Soheilifar MH, Javeri A, Amini H, Taha MF
Human fat-derived stem cells can be turned into dopamine-producing cells in the lab using specific growth factors, and these cells release dopamine when stimulated, suggesting potential for treating Parkinson's disease.
- Fat stem cells became dopamine-making neurons in lab tests
- Cells released dopamine when triggered by electrical stimulation
- Key genes for dopamine production were activated
- About 28% of cells made dopamine protein (TH)
- This approach could help develop cell therapies for Parkinson's
Whole transcriptome profiling of Late-Onset Alzheimer's Disease patients provides insights into the molecular changes involved in the disease.
Annese A, Manzari C, Lionetti C, Picardi E, Horner DS, Chiara M, Caratozzolo MF, Tullo A, Fosso B, Pesole G, D'Erchia AM
This study found that genes and microRNAs involved in memory and brain function, including NR4A2, are disrupted in Alzheimer's disease brains, with miR-184 directly targeting NR4A2, suggesting a potential mechanism affecting cognition. These changes were seen in key brain regions linked to memory and are consistent with Alzheimer's progression.
- NR4A2 is targeted by miR-184 in Alzheimer’s brain
- NR4A2 levels are linked to memory and cognitive function
- miR-184 and NR4A2 are inversely regulated in Alzheimer’s
- Changes in brain gene expression are region-specific
- RNA editing is reduced in Alzheimer’s hippocampus
miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation.
De Gregorio R, Pulcrano S, De Sanctis C, Volpicelli F, Guatteo E, von Oerthel L, Latagliata EC, Esposito R, Piscitelli RM, Perrone-Capano C, Costa V, Greco D, Puglisi-Allegra S, Smidt MP, di Porzio U, Caiazzo M, Mercuri NB, Li M, Bellenchi GC
miR-34b/c boosts the creation of dopamine-producing brain cells by regulating Wnt1 and working with key genes like NURR1, significantly increasing the efficiency of turning other cells into functional dopaminergic neurons.
- miR-34b/c enhances dopamine neuron formation
- Works with NURR1 to improve cell conversion
- Increases yield of functional dopaminergic neurons
- Promotes cell cycle exit and neuron maturation
- May help develop better cell-based therapies
Ultrasound-triggered effects of the microbubbles coupled to GDNF- and Nurr1-loaded PEGylated liposomes in a rat model of Parkinson's disease.
Yue P, Gao L, Wang X, Ding X, Teng J
Delivering GDNF and Nurr1 genes using ultrasound-triggered liposomes improved movement and protected dopamine neurons in a rat model of Parkinson's disease, with the combined treatment working better than either gene alone.
- Combining GDNF and Nurr1 genes enhanced brain protection and movement recovery
- Ultrasound helped deliver treatments precisely to the brain
- The dual-gene approach reduced symptoms more than single treatments
- This strategy could lead to better Parkinson's therapies in the future
Correlation between Nurr1 expression and drug resistance in the brain of rats with epilepsy.
Li HY, Liu F, Wang HR
In rats with drug-resistant epilepsy, higher levels of the Nurr1 protein in the hippocampus are linked to increased expression of proteins that cause resistance to anti-seizure medications. This suggests Nurr1 may play a key role in making epilepsy harder to treat.
- Nurr1 levels rise in the hippocampus of drug-resistant rats
- High Nurr1 correlates with more drug-resistance proteins
- Nurr1 may drive resistance to common epilepsy drugs
- Targeting Nurr1 could help overcome drug resistance
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
Rhynchophylline may help reduce ketamine addiction by restoring levels of a microRNA called miR-331-5p, which controls the Nurr1 protein—important for brain function and linked to NR4A2-related disorders. This suggests a potential pathway for treating NR4A2-related conditions through similar molecular targets.
- miR-331-5p regulates Nurr1, a protein linked to NR4A2
- Rhynchophylline boosts miR-331-5p and Nurr1 levels
- Nurr1 and BDNF are both affected in the same direction
- The pathway may involve CREB phosphorylation
- Findings suggest a possible treatment route for NR4A2 disorders
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 reversed ketamine-induced reward behavior in rats by normalizing levels of p-CREB, Nurr1, and BDNF in the hippocampus, suggesting it may reduce addictive behaviors by targeting key brain pathways involved in reward and plasticity.
- Rhynchophylline reduced ketamine's rewarding effects in rats
- It lowered elevated levels of p-CREB, Nurr1, and BDNF in the hippocampus
- These proteins are linked to addiction-related brain changes
- The findings suggest a potential mechanism for treating substance use
- Nurr1 is the same protein affected in NR4A2-related syndrome
Nurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory factors in the transwell coculture system of neural stem cells and microglia.
Chen XX, Qian Y, Wang XP, Tang ZW, Xu JT, Lin H, Yang ZY, Song XB, Lu D, Guo JZ, Bian LG, Li Y, Zhou L, Deng XL
Nurr1 helps neural stem cells become dopamine-producing brain cells and reduces harmful inflammation from immune cells in the brain. This suggests that boosting Nurr1 in stem cells could improve cell therapy for Parkinson’s disease.
- Nurr1 helps stem cells turn into dopamine neurons
- Nurr1 reduces brain inflammation from immune cells
- Boosting Nurr1 may improve stem cell transplants for Parkinson’s
- This supports using Nurr1-enhanced cells in future treatments
Cilostazol Mediated Nurr1 and Autophagy Enhancement: Neuroprotective Activity in Rat Rotenone PD Model.
Hedya SA, Safar MM, Bahgat AK
Cilostazol protects brain cells in a rat model of Parkinson's disease by boosting Nurr1, reducing inflammation and cell death, and enhancing autophagy—a process that clears damaged cellular components. These effects together improved motor function and preserved dopamine-producing neurons.
- Cilostazol boosts Nurr1, a key protein for dopamine neuron health
- It reduces brain inflammation and prevents cell death
- Cilostazol enhances autophagy, helping clear cellular damage
- Improved movement and dopamine levels were seen in rats
- The drug targets multiple pathways linked to Parkinson’s
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
NR4A2 is part of an early transcriptional program that primes multipotent cells to become B cells, and blocking NR4A2 stops this process. This three-step network involving NR4A2 and other genes helps guide cell fate decisions in blood development.
- NR4A2 acts early in B-cell development, before major B-cell genes turn on
- Blocking NR4A2 stops cells from becoming B cells
- A three-step gene network guides blood cell fate decisions
- Findings match what happens in real bone marrow cells
- This could help understand or treat blood disorders
Conserved Upstream Regulatory Regions in Mammalian Tyrosine Hydroxylase.
Wang M, Fones L, Cave JW
The study identifies key regulatory regions upstream of the tyrosine hydroxylase (TH) gene that control its activity in brain cells, including a newly discovered role for the CTCF protein in regulating TH expression in the forebrain. These regions are conserved across mammals and bind important transcription factors like NURR1, which is directly linked to NR4A2-related syndrome.
- Five conserved DNA regions regulate TH gene activity in brain cells
- NURR1 and other key factors bind to these regulatory regions
- CTCF is a newly identified regulator of TH in the forebrain
- These findings reveal how TH expression is controlled in catecholaminergic neurons
- The regulatory architecture is conserved across mammals
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
Certain dietary compounds like DHA and curcumin can activate skin repair genes in people missing key skin barrier genes, potentially reducing inflammation and improving skin health in conditions like psoriasis. These nutrients work through the vitamin D receptor and influence genes linked to skin repair and immune response.
- DHA and curcumin boost skin repair genes in people missing LCE3B/C
- These nutrients reduce inflammation by blocking key stress pathways
- They activate NR4A2/NURR1, a gene linked to skin barrier control
- Dietary VDR ligands may help treat mild to moderate psoriasis
- Findings suggest a role for nutrition in managing skin repair
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 found that specific microRNAs and genes, including NR4A2, are linked to kidney problems in a mouse model of megabladder, suggesting they may play a role in congenital obstructive nephropathy.
- NR4A2 is a key transcription factor linked to kidney development in this model
- Three microRNAs were identified as potentially important in kidney disease
- NR4A2 regulates Vegfa, a gene involved in blood vessel formation
- The findings may help explain how kidney function is disrupted in megabladder
- This provides a potential pathway for future treatments
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
MicroRNA-137 boosts the growth and blood vessel formation of endothelial progenitor cells in mice after stroke by suppressing NR4A2, which activates the Notch signaling pathway. This suggests a potential therapeutic strategy to improve recovery after stroke by targeting this molecular pathway.
- miR-137 increases blood vessel-forming cell growth after stroke
- miR-137 works by turning down NR4A2
- NR4A2 suppression improves cell survival and function
- The Notch pathway is involved in this repair process
- Findings may inform future stroke recovery treatments