BMS-470539 Attenuates Oxidative Stress and Neuronal Apoptosis via MC1R/cAMP/PKA/Nurr1 Signaling Pathway in a Neonatal Hypoxic-Ischemic Rat Model.
Yu S, Doycheva DM, Gamdzyk M, Gao Y, Guo Y, Travis ZD, Tang J, Chen WX, Zhang JH
BMS-470539, a drug that activates the MC1R receptor, reduces brain damage and improves brain function in newborn rats after oxygen deprivation. It works by boosting the Nurr1 protein, which protects neurons from stress and death, and this effect depends on a specific signaling pathway involving cAMP and PKA.
- BMS-470539 reduces brain injury after oxygen loss in newborn rats
- It protects neurons by reducing oxidative stress and cell death
- The drug works through the MC1R/cAMP/PKA/Nurr1 pathway
- Blocking Nurr1 or MC1R stops the drug’s benefits
- Early treatment may help infants with brain injury from oxygen lack
Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution.
Honkova K, Rossnerova A, Chvojkova I, Milcova A, Margaryan H, Pastorkova A, Ambroz A, Rossner P, Jirik V, Rubes J, Sram RJ, Topinka J
Air pollution differences between cities are linked to changes in DNA methylation across the human genome, including in genes related to brain function and neurodegenerative diseases, such as NR4A2. These changes may reflect environmental impacts on gene regulation with potential long-term health consequences.
- Air pollution differences alter DNA methylation patterns in humans
- NR4A2, a gene linked to brain health, shows methylation changes
- Affected genes are tied to neurodegenerative diseases and dopamine systems
- Changes in methylation may impact neuronal function and cell adhesion
- Axon guidance and brain-related pathways are significantly affected
Potential role of inducible GPR3 expression under stimulated T cell conditions.
Shiraki H, Tanaka S, Guo Y, Harada K, Hide I, Yasuda T, Sakai N
GPR3 is rapidly turned on in T cells when they are activated and helps prevent excessive immune responses by keeping effector T cells in check. This process involves NR4A2, a gene linked to neurological and immune disorders, suggesting a potential connection between immune regulation and NR4A2-related conditions.
- GPR3 turns on quickly after T cell activation
- GPR3 regulates NR4A2, a gene tied to NR4A2-related syndrome
- Without GPR3, T cells become overactive spontaneously
- GPR3 helps control immune overactivation through NR4A2
- This pathway may influence immune and neurological health
Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.
Sharma S, Shen T, Chitranshi N, Gupta V, Basavarajappa D, Sarkar S, Mirzaei M, You Y, Krezel W, Graham SL, Gupta V
Retinoid X receptors (RXRs) are important regulators of gene expression in the brain and are involved in conditions like Parkinson's and Alzheimer's disease. Targeting RXRs with drugs shows protective effects in animal models of brain injury, suggesting potential treatment strategies.
- RXRs regulate genes critical for brain development and function
- Abnormal RXR signaling is linked to brain diseases like Parkinson's
- Drug targeting of RXRs protects neurons in animal models
- Different RXR forms may respond differently to treatments
Synergistic Effects of Combined Nurr1 Overexpression and Natural Inducers on the More Efficient Production of Dopaminergic Neuron-Like Cells From Stem Cells.
Beiki R, Khaghani M, Esmaeili F, Dehghanian F
Combining Nurr1 gene overexpression with a brain extract significantly boosts the production of dopamine-producing neurons from stem cells, suggesting a promising approach for treating Parkinson's disease and potentially informing therapies for NR4A2-related syndromes.
- Nurr1 and brain extract together enhance dopamine neuron formation
- Stem cells developed neuron-like features and dopamine markers
- Best results seen after two weeks of differentiation
- This synergy may improve cell replacement strategies
- Findings could guide future treatments for NR4A2-related conditions
Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice.
Liu L, Wang H, Chen X, Zhang Y, Li W, Rao X, Liu Y, Zhao L, Pu J, Gui S, Yang D, Fang L, Xie P
This study found that gut microbiota from people with depression alters gene activity in the mouse brain, particularly affecting genes involved in brain development and inflammation. A specific network involving the NR4A2 gene and other RNA molecules may play a key role in these changes, suggesting a potential link between gut health and neurodevelopmental disorders.
- Gut microbes from depressed people alter brain gene activity in mice
- NR4A2 is part of a regulatory network linked to brain development
- This network may explain how gut health affects brain function
- The findings point to possible new treatments targeting gut-brain pathways
Developmental Patterning and Neurogenetic Gradients of Nurr1 Positive Neurons in the Rat Claustrum and Lateral Cortex.
Fang C, Wang H, Naumann RK
Nurr1-expressing neurons in the rat claustrum and nearby cortex develop in a specific sequence during embryonic days E13.5 to E17.5, with distinct birth dates for different subregions, revealing a precise developmental timeline that may help explain how these neurons form and function in brain circuits.
- Nurr1 neurons in claustrum and cortex form in a specific order over several embryonic days
- Dorsal endopiriform neurons are born first (E13.5–E14.5)
- Claustrum and cortical Nurr1 neurons appear in waves from E14.5 to E17.5
- Development follows clear ventral-to-dorsal and posterior-to-anterior patterns
- These findings map the embryonic origin of Nurr1 neurons in rodent brain
Nuclear receptors of NR1 and NR4 subfamilies in the regulation of microglial functions and pathology.
Katsuki H
NR4A2 (also known as Nurr1) and other nuclear receptors in the NR1 and NR4 families help control microglia, the brain's immune cells, reducing harmful inflammation and boosting protective functions. Activating these receptors may improve outcomes in brain disorders like Parkinson’s and Alzheimer’s, suggesting potential treatments for NR4A2-related syndromes.
- NR4A2/Nurr1 regulates microglial activity in the brain
- Activating NR4A2 reduces brain inflammation
- NR4A2 activation may improve brain function in neurological diseases
- Drugs targeting NR4A2 could be promising for treatment
- Microglia become more protective when NR4A2 is activated
Exosomal lncRNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1)contributes to the progression of allergic rhinitis via modulating microRNA-511/Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) axis.
Wang T, Cai W, Wu Q, Chen D, Wang P, Xu Z
Exosomes carrying a long RNA called NEAT1 worsen allergic rhinitis by suppressing NR4A2, a gene important for controlling inflammation and mucus production. This happens through a chain reaction where NEAT1 blocks a microRNA (miR-511), which normally keeps NR4A2 active. Targeting this pathway could lead to new treatments for allergic rhinitis.
- NEAT1 in exosomes increases allergy symptoms
- NEAT1 blocks miR-511, reducing NR4A2 activity
- Lower NR4A2 leads to more inflammation and mucus
- Blocking NEAT1 or boosting miR-511 reduces symptoms
- This pathway may be a target for new allergy treatments
Variability in Behavioral Phenotypes after Forced Swimming-Induced Stress in Rats Is Associated with Expression of the Glucocorticoid Receptor, Nurr1, and IL-1β in the Hippocampus.
Ruiz-Sánchez E, López-Ramírez AM, Ruiz-Chow Á, Calvillo M, Reséndiz-Albor AA, Anguiano B, Rojas P
Rats that showed high immobility after stress (vulnerable) had higher levels of glucocorticoid receptor, Nurr1, and IL-1β proteins in the hippocampus compared to resilient rats, suggesting these molecules are linked to stress response differences. This points to potential biological markers for stress vulnerability.
- Vulnerable rats had higher stress-related proteins in the brain
- Nurr1 and GR levels differed between stress-resilient and vulnerable rats
- IL-1β was elevated in vulnerable rats after stress
- These proteins may serve as biomarkers for stress susceptibility
- Findings highlight brain mechanisms behind stress coping differences
Nr4a2 Transcription Factor in Hippocampal Synaptic Plasticity, Memory and Cognitive Dysfunction: A Perspective Review.
Català-Solsona J, Miñano-Molina AJ, Rodríguez-Álvarez J
NR4A2 plays a key role in regulating synaptic plasticity and memory in the hippocampus, and its dysfunction may contribute to cognitive problems seen in brain disorders. This suggests NR4A2 could be a promising target for treating cognitive symptoms in neurological conditions.
- NR4A2 is critical for memory and synaptic function in the hippocampus
- Low NR4A2 activity may lead to cognitive decline
- NR4A2 could be a new target for treating memory disorders
- Research is uncovering how NR4A2 affects brain circuitry
NR4A2 alleviates cardiomyocyte loss and myocardial injury in rats by transcriptionally suppressing CCR5 and inducing M2 polarization of macrophages.
Miao H, Li X, Zhou C, Liang Y, Li D, Ji Q
NR4A2 protects heart cells in diabetic rats by reducing inflammation and promoting repair-friendly immune cells, partly by turning down a harmful gene called CCR5. Boosting NR4A2 activity helps preserve heart function and limits damage.
- NR4A2 reduces heart damage in diabetic rats
- NR4A2 turns down CCR5, a gene that drives inflammation
- NR4A2 promotes healing immune cells in the heart
- Blocking CCR5 mimics NR4A2’s protective effects
- NR4A2 may help protect heart cells from high glucose
The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells.
Wang N, Ji X, Wu Y, Zhou S, Peng H, Wang J, Yu S, Zhang J
Astrocytes can be efficiently turned into dopamine-producing neurons using specific genetic and chemical treatments, making them a strong candidate for cell therapy in Parkinson's disease. Mesenchymal stem cells showed much lower conversion efficiency, suggesting astrocytes are better suited for this approach.
- Astrocytes convert well into dopamine neurons
- Genetic factors (MLN) boost conversion efficiency
- Chemical and morphogen treatments help astrocyte conversion
- Mesenchymal stem cells convert poorly
- Astrocytes show unique potential for Parkinson's therapy
Current Status of the Hypothesis of a Claustro-Insular Homolog in Sauropsids.
Puelles L
This paper explores the evolutionary origin of brain regions linked to the NR4A2 gene, suggesting that a part of the avian brain similar to the mammalian claustro-insular complex may exist, with NR4A2 marking a specific cell group. The findings support the idea that this brain region is ancient and conserved across vertebrates, including birds and reptiles.
- NR4A2 marks a deep claustral cell group in mammals
- Avian brain has a similar NR4A2-expressing region
- This suggests a conserved claustro-insular brain structure across species
- The findings may help understand NR4A2-related brain development
- Evolutionary insights could inform future research on NR4A2 syndromes
NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast.
de Alwis N, Beard S, Binder NK, Pritchard N, Kaitu'u-Lino TJ, Walker SP, Stock O, Groom KM, Petersen S, Henry A, Said JM, Seeho S, Kane SC, Tong S, Hannan NJ
NR4A2 levels in placental tissue are not changed in pregnancies affected by growth restriction or preeclampsia, but are reduced under low oxygen conditions in placental cells. This suggests that the increased NR4A2 seen in maternal blood likely comes from outside the placenta and may reflect a stress response rather than placental dysfunction.
- Placental NR4A2 is not elevated in growth restriction or preeclampsia
- Low oxygen reduces NR4A2 in placental cells
- Circulating NR4A2 likely comes from outside the placenta
- NR4A2 loss under hypoxia affects stress and inflammation genes
- No effect on key placental angiogenic factors
Development and Profiling of Inverse Agonist Tools for the Neuroprotective Transcription Factor Nurr1.
Zaienne D, Willems S, Schierle S, Heering J, Merk D
Researchers developed new compounds that reduce the activity of the Nurr1 protein, which is linked to brain health and neurodegenerative diseases. These compounds help study how Nurr1 affects brain inflammation and may guide future treatments for conditions like Parkinson’s, especially in people with NR4A2-related syndromes.
- New compounds turn down Nurr1 activity by over 90%
- They target Nurr1 in ways that may reduce brain inflammation
- These tools help study Nurr1’s role in disease and therapy
- Findings may inform treatments for NR4A2-related disorders
α-Synuclein Induces the GSK-3-Mediated Phosphorylation and Degradation of NURR1 and Loss of Dopaminergic Hallmarks.
García-Yagüe ÁJ, Lastres-Becker I, Stefanis L, Vassilatis DK, Cuadrado A
In Parkinson's disease, a toxic protein called alpha-synuclein triggers a chain reaction that destroys NURR1, a critical protein for maintaining healthy dopamine-producing brain cells. This happens when alpha-synuclein activates another enzyme, GSK-3, which tags NURR1 for breakdown by the cell's waste system.
- Alpha-synuclein harms dopamine neurons by destroying NURR1
- GSK-3 enzyme tags NURR1 for destruction
- NURR1 is broken down by the cell's recycling system
- A specific part of NURR1 is targeted by GSK-3
- This process may explain dopamine neuron loss in Parkinson’s
The Impact of CB1 Receptor on Nuclear Receptors in Skeletal Muscle Cells.
Haddad M
CB1 receptors in skeletal muscle cells regulate the activity of NR4A1 and NR4A3 genes, with potential implications for muscle function and disease. Blocking CB1 receptors reduces expression of NR4A1, NR4A2, and NR4A3, suggesting a key role in gene control.
- CB1 receptors affect NR4A1 and NR4A3 gene levels in muscle cells
- Activating CB1 increases NR4A1 and NR4A3 expression
- Blocking CB1 reduces NR4A1, NR4A2, and NR4A3 levels
- This pathway may influence muscle biology and disease
- Findings suggest possible therapeutic targets for muscle-related conditions
Selymatra: A web application for protein-profiling analysis of mass spectra.
Nardone D, Ciaramella A, Cerreta M, Pulcrano S, Bellenchi GC, Leone L, Manco G, Febbraio F
This web tool automates protein analysis from mass spectrometry data, helping identify proteins in complex samples. It was tested in a cell model with a tagged NURR1 protein and successfully detected it, showing potential for studying NR4A2/NURR1-related conditions.
- Automates protein identification from mass spectrometry data
- Successfully detected a tagged NURR1 protein in cell models
- Can help analyze protein changes in NR4A2-related disorders
- Designed for use with complex biological samples like tissues and cells
A systematic dissection of human primary osteoblasts in vivo at single-cell resolution.
Gong Y, Yang J, Li X, Zhou C, Chen Y, Wang Z, Qiu X, Liu Y, Zhang H, Greenbaum J, Cheng L, Hu Y, Xie J, Yang X, Li Y, Bai Y, Wang YP, Chen Y, Tan LJ, Shen H, Xiao HM, Deng HW
This study identifies a rare subtype of human bone-forming cells that produce high levels of NR4A2, a gene linked to neurological disorders. These cells appear to play a key role in bone development and may also influence blood vessel and blood cell formation. The findings highlight important differences between human and mouse bone cells, stressing the need for human-focused research.
- A rare osteoblast subtype produces high NR4A2 levels
- This subtype helps form mature bone cells and may regulate blood vessels and blood cells
- Human bone cells differ significantly from mouse cells
- NR4A2 expression confirmed in mouse bone cells
- Findings support studying human bone biology directly
Minireview: What is Known about SUMOylation Among NR4A Family Members?
Dodat F, Mader S, Lévesque D
SUMOylation regulates the activity of NR4A family proteins, including NURR1 (NR4A2), by altering their ability to control gene expression, which may influence neurological and inflammatory processes relevant to NR4A2-related syndrome.
- SUMOylation affects NURR1's ability to regulate genes
- This modification influences neuronal and inflammatory pathways
- No known natural ligands exist for NR4A receptors
- SUMOylation is a reversible process that fine-tunes protein function
- Findings may inform future therapies targeting NURR1 activity
Reconstruction of the Cytokine Signaling in Lysosomal Storage Diseases by Literature Mining and Network Analysis.
Parolo S, Tomasoni D, Bora P, Ramponi A, Kaddi C, Azer K, Domenici E, Neves-Zaph S, Lombardo R
This study identifies key inflammatory signaling pathways in three lysosomal storage diseases linked to sphingolipid buildup, highlighting NR4A2 as a potential regulator of cytokine activity in immune cells, which may point to new anti-inflammatory treatment targets.
- NR4A2 is a candidate regulator of inflammation in Gaucher disease
- Inflammatory signaling involves multiple cell-specific pathways
- Findings may lead to new anti-inflammatory therapies for LSDs
- Cytokine networks are complex and involve STAT2 and JUN
- Systems biology reveals potential drug targets in lysosomal diseases
Propofol protects H9C2 cells against hypoxia/reoxygenation injury through miR-449a and NR4A2.
Qian Q, Xie Y
Propofol protects heart cells from injury caused by low oxygen and recovery by boosting NR4A2, a gene linked to NR4A2-related syndrome, through a microRNA called miR-449a. This suggests propofol may help reduce cell damage in conditions involving oxygen deprivation.
- Propofol reduces heart cell damage from low oxygen
- It works by increasing NR4A2 levels
- miR-449a normally blocks NR4A2, but propofol reduces it
- NR4A2 is directly linked to NR4A2-related syndrome
- Findings may inform protective strategies in oxygen-related injuries
Association Between NR4A2 Gene Polymorphism and Depressive Symptoms and Antidepressant Effect.
Song X, Sun N, Zhang A, Lei L, Li X, Liu Z, Wang Y, Yang C, Zhang K
Certain variations in the NR4A2 gene are linked to specific depressive symptoms like slowed movements and physical complaints, and one variation may predict how well a person responds to antidepressant treatment.
- NR4A2 gene changes affect depression symptoms
- Some variants increase physical slowing and gut issues
- One variant predicts better antidepressant response
- These findings may guide personalized treatment
- NR4A2 plays a key role in brain dopamine function
Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis.
Zhao Z, Fu Q, Hu L, Liu Y
This study identified NR4A2 as one of 10 hub genes linked to intimal hyperplasia in arteriovenous fistulas, a condition involving abnormal blood vessel thickening. NR4A2 is part of the MAPK signaling pathway, which plays a key role in cell growth and inflammation, suggesting it could be a target for preventing fistula failure.
- NR4A2 is a hub gene in vascular remodeling after fistula creation
- It is linked to the MAPK signaling pathway, driving cell proliferation
- Low NR4A2 levels correlate with increased inflammation
- NR4A2 may be a therapeutic target to prevent fistula stenosis
- Findings are based on human gene expression data and pathway analysis
Bisphenol A exposure induces neurobehavioral deficits and neurodegeneration through induction of oxidative stress and activated caspase-3 expression in zebrafish brain.
Sahoo PK, Aparna S, Naik PK, Singh SB, Das SK
Chronic exposure to bisphenol A (BPA) causes motor problems, brain cell damage, and signs of Parkinson's-like disease in zebrafish by increasing oxidative stress and cell death. BPA lowers levels of protective brain proteins like Nurr1 and raises harmful proteins linked to Parkinson's, suggesting it may worsen neurodegeneration.
- BPA causes motor and behavioral problems in zebrafish
- BPA increases brain cell death and oxidative stress
- BPA reduces Nurr1, a key protein in NR4A2-related syndromes
- BPA raises levels of Parkinson’s-related proteins like alpha-synuclein
- Zebrafish show Parkinsonism-like brain changes after BPA exposure
Modified UCN2 peptide treatment improves skeletal muscle mass and function in mouse models of obesity-induced insulin resistance.
Borg ML, Massart J, De Castro Barbosa T, Archilla-Ortega A, Smith JAB, Lanner JT, Alsina-Fernandez J, Yaden B, Culver AE, Karlsson HKR, Brozinick JT, Zierath JR
Modified UCN2 peptides improve skeletal muscle mass and function in mice with obesity or immobilization, suggesting a potential treatment for muscle wasting in metabolic diseases like type 2 diabetes.
- UCN2 treatment increased muscle mass in obese mice
- It boosted protein synthesis and reduced muscle breakdown pathways
- It preserved muscle strength during disuse from casting
- Both modified UCN2 forms improved lean mass and muscle function
- NR4A2 expression increased, linking to muscle anabolism
Nurr1 repression mediates cardinal features of Parkinson's disease in α-synuclein transgenic mice.
Argyrofthalmidou M, Spathis AD, Maniati M, Poula A, Katsianou MA, Sotiriou E, Manousaki M, Perier C, Papapanagiotou I, Papadopoulou-Daifoti Z, Pitychoutis PM, Alexakos P, Vila M, Stefanis L, Vassilatis DK
Alpha-synuclein buildup and reduced Nurr1 levels together cause Parkinson's-like symptoms and brain damage in mice, showing that Nurr1 loss is a key step in disease development. This suggests that protecting or boosting Nurr1 could help treat Parkinson's and related conditions.
- Alpha-synuclein and Nurr1 levels oppose each other with age.
- Low Nurr1 plus high alpha-synuclein causes severe Parkinson's-like symptoms.
- Nurr1 loss is required for disease to develop in this model.
- Boosting Nurr1 may protect brain cells in Parkinson's.
- This mechanism may apply to human NR4A2-related disorders.
Conditional deficiency of m6A methyltransferase Mettl14 in substantia nigra alters dopaminergic neuron function.
Teng Y, Liu Z, Chen X, Liu Y, Geng F, Le W, Jiang H, Yang L
Disabling a key enzyme that adds a chemical tag (m6A) to RNA in dopamine-producing brain cells harms their function, leading to movement problems and reduced dopamine production in mice. This tag is crucial for maintaining the activity of genes that control dopamine neurons, including the NR4A2 gene (Nurr1).
- m6A RNA tagging is essential for dopamine neuron function
- Loss of m6A leads to movement and motor issues in mice
- NR4A2 (Nurr1) gene expression drops without m6A
- Dopamine-making enzyme TH is reduced
- Brain inflammation increases in affected areas
Trophoblast glycoprotein is a marker for efficient sorting of ventral mesencephalic dopaminergic precursors derived from human pluripotent stem cells.
Yoo JE, Lee DR, Park S, Shin HR, Lee KG, Kim DS, Jo MY, Eom JH, Cho MS, Hwang DY, Kim DW
This study identifies a surface marker called TPBG that helps isolate pure populations of dopamine-producing brain cells from stem cells, leading to better outcomes in Parkinson's disease models. The sorted cells form more functional dopamine neurons and reduce unwanted cell growth in transplants.
- TPBG marks dopamine precursor cells from stem cells
- Sorting using TPBG yields highly pure dopamine cells
- Transplanted TPBG+ cells improve Parkinson's symptoms in animals
- Fewer uncontrolled dividing cells in TPBG+ grafts
- Potential for safer, more effective Parkinson's cell therapy
Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation.
Cui X, Pertile RAN, Du Z, Wei W, Sun Z, Eyles DW, Kesby JP
HOTAIRM1, a long non-coding RNA, is essential for the proper development and maturation of dopamine neurons. Reducing HOTAIRM1 levels disrupts key genes needed for dopamine neuron formation, impairing their differentiation.
- HOTAIRM1 supports dopamine neuron development
- Lower HOTAIRM1 reduces critical dopamine genes
- Disruption leads to faulty neuron maturation
- Findings may relate to neurodevelopmental disorders
Construction of Competing Endogenous RNA Networks Incorporating Transcription Factors to Reveal Differences in Granulosa Cells from Patients with Endometriosis.
Wu R, Li J, Li J, Zhang N, Zhou W, Ren L, Chen Q, Li Y
This study identified a network of interacting RNAs and transcription factors in ovarian cells from women with endometriosis-related infertility, including NR4A2, a gene linked to neurological development and function. The network highlights potential molecular disruptions involving NR4A2, which may contribute to infertility in endometriosis. While not directly about NR4A2-related syndrome, the findings suggest NR4A2's role in cellular regulation may extend beyond the brain.
- NR4A2 was found in a key regulatory RNA network in endometriosis
- The network includes miRNAs, lncRNAs, and transcription factors
- NR4A2 may be dysregulated in reproductive cells
- Findings could inform broader understanding of NR4A2 function
- No direct link to NR4A2-related neurodevelopmental syndrome