The Nurr1 ligand indole acetic acid hydrazide loaded onto ZnFe2O4 nanoparticles suppresses proinflammatory gene expressions in SimA9 microglial cells.
Qasim R, Thiab TA, Alhindi T, Al-Hunaiti A, Imraish A
A compound called IAAH, delivered using special nanoparticles, activates the Nurr1 protein in brain immune cells, reducing the production of harmful inflammatory signals. This approach may help calm chronic brain inflammation linked to neurological disorders.
- IAAH activates Nurr1 to reduce brain inflammation
- Nanoparticles improve delivery and effectiveness
- Targets key inflammatory genes like IL-6 and TNF-α
- Potential for treating neuroinflammatory conditions
- Uses a targeted delivery system to boost therapy
Gangliosides in neural stem cell fate determination and nerve cell specification--preparation and administration.
Itokazu Y, Ariga T, Fuchigami T, Li D
Gangliosides GD3 and GM1 play critical roles in maintaining neural stem cells and guiding their development into nerve cells, with GM1 specifically promoting the formation of dopamine-producing neurons through epigenetic regulation. Administering these molecules can restore stem cell function and improve neuronal outcomes in mouse models.
- GD3 supports neural stem cell survival and self-renewal
- GM1 boosts neuron development and dopamine gene activation
- GM1 works by modifying gene expression through epigenetic changes
- Gangliosides act on membranes in the cell's nucleus, mitochondria, and surface
- Direct administration of GD3/GM1 improves brain cell function in mice
Transcription Factor-Mediated Generation of Dopaminergic Neurons from Human iPSCs-A Comparison of Methods.
McDonald KO, Lyons NMA, Gray LKC, Xu JB, Schoderboeck L, Hughes SM, Basak I
This study developed a faster and more efficient method to create human dopaminergic neurons from skin cells using transcription factors and small molecules, producing over 85% dopaminergic neurons in just three weeks. The approach avoids viral integration by using a safe genetic location, improving safety and consistency.
- Creates dopaminergic neurons in three weeks, not months
- Over 85% of neurons are dopaminergic
- Uses safer genetic methods without viral integration
- Combines transcription factors and small molecules for best results
- May help study and treat NR4A2-related disorders
Impact of food additives on neurodevelopmental processes in zebrafish (Danio rerio): Exploring circadian clock genes and dopamine system.
Christy LD, Vignesh K, Nellore J, Tippabathani J
Food additives like aspartame and tartrazine disrupt brain development in zebrafish, affecting genes linked to the circadian clock and dopamine signaling, leading to abnormal movement, heart rate, and brain changes. These effects occur at levels below current safety limits and suggest potential risks to human neurodevelopment, especially during pregnancy.
- Additives alter dopamine and circadian genes in zebrafish
- Exposure causes movement and heart rate changes
- Effects seen at safe levels, raising concern for early development
- Zebrafish findings may reflect human neurodevelopment risks
- Supports re-evaluating food additive safety during pregnancy
NR4A2 as a Novel Target Gene for Developmental and Epileptic Encephalopathy: A Systematic Review of Related Disorders and Therapeutic Strategies.
Gabaldon-Albero A, Mayo S, Martinez F
NR4A2 gene variants cause a serious neurological condition affecting development, movement, language, and epilepsy, with symptoms appearing from infancy to young adulthood. The review supports testing NR4A2 as a top priority in genetic testing for children with unexplained developmental delay and epilepsy.
- NR4A2 variants cause developmental delay and intellectual disability
- Epilepsy occurs in 42% of patients, often drug-resistant
- Language and movement problems are common and underdiagnosed
- NR4A2 should be tested early in developmental and epileptic encephalopathy
- New therapies targeting NR4A2 are being explored
Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors.
Ho DH, Kim H, Nam D, Seo MK, Park SW, Son I
Mutant LRRK2 in astrocytes harms brain cells by triggering inflammation and disrupting dopamine production, which may worsen Parkinson's disease. This effect happens through toxic signals released by astrocytes carrying the G2019S mutation.
- G2019S-LRRK2 in astrocytes causes inflammation and reduces survival signals
- Astrocytes with the mutation release harmful factors that damage dopamine-producing neurons
- Dopamine production and transport are impaired in nearby neurons
- This mechanism may accelerate Parkinson’s disease progression
- Targeting astrocyte inflammation could be a new treatment strategy
Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice.
Kinoshita K, Motomura K, Ushida K, Hirata Y, Konno A, Hirai H, Kotani S, Hitora-Imamura N, Kurauchi Y, Seki T, Katsuki H
Overexpressing the Nurr1 protein in brain cells that control movement helps protect nerve pathways after a stroke-like brain bleed in mice, reducing motor problems. This effect happens by strengthening nerve fibers in the brain's motor circuit, not by reducing brain inflammation or cell death.
- Nurr1 overexpression improves motor recovery after brain bleeds in mice
- It protects nerve fibers in the motor pathway without reducing brain inflammation
- Nurr1 boosts protective signaling in motor brain cells
- Nurr1 ligands also activate the same protective brain pathways
- This suggests targeting Nurr1 could help treat motor symptoms in NR4A2-related conditions
Corrigendum to "Nurr1: A vital participant in the TLR4-NF-κB signal pathway stimulated by a-synuclein in BV-2 cells" [Neuropharmacol. (2019) 144 388-399] doi:10.1016/j.neuropharm.2018.04.008.
Shao QH, Yan WF, Zhang Z, Ma KL, Peng SY, Cao YL, Yuan YH, Chen NH
Nurr1 reduces inflammation in brain cells exposed to alpha-synuclein, a protein linked to neurodegeneration, suggesting it may protect against brain damage in NR4A2-related disorders.
- Nurr1 dampens harmful brain inflammation
- Alpha-synuclein triggers inflammation via NF-κB
- Nurr1 blocks this inflammatory pathway
- This may protect neurons in NR4A2-related conditions
Differentiation of neural stem cells from human olfactory mucosa into dopaminergic neuron-like cells.
Ertem T, Uysal O
Human olfactory mucosa neural stem cells can be turned into dopamine-producing cells in the lab, offering a potential source for cell-based treatments in Parkinson's disease and similar conditions.
- Olfactory stem cells can become dopamine-making neurons
- Cells express key genes like NURR1 and TH after differentiation
- These cells are easy to collect and grow in culture
- They show promise for treating Parkinson's disease
- Results support future cell replacement therapies
Nur77 Mediates Anaphylaxis by Regulating miR-21a.
Jo H, Jeoung J, Shim K, Jeoung D
Nur77, a gene related to NR4A2, plays a key role in triggering anaphylaxis by controlling immune responses through a feedback loop with miR-21a. Blocking Nur77 or boosting miR-21a reduces allergic reactions in cell and animal models, suggesting potential new treatments for severe allergies.
- Nur77 drives anaphylaxis in immune cells
- miR-21a suppresses Nur77 and reduces allergic reactions
- Targeting Nur77 or miR-21a may treat severe allergies
- Nur77 activity is controlled by c-JUN in allergic responses
Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1.
Chen N, Zhou H, He B, Peng S, Ding F, Liu QH, Ma Z, Liu W, Xu B
Melatonin helps protect neural stem cells from manganese damage by activating the Nurr1 protein, which restores normal cell division and prevents developmental delays. This suggests melatonin could be a potential therapy for neurodevelopmental issues linked to manganese exposure.
- Melatonin protects brain cell development from manganese damage
- It works by activating the Nurr1 protein
- Nurr1 helps restart cell division blocked by manganese
- Blocking Nurr1 reduces melatonin's protective effect
- Findings may lead to treatments for NR4A2-related disorders
Relapse to cocaine seeking is regulated by medial habenula NR4A2/NURR1 in mice.
Childs JE, Morabito S, Das S, Santelli C, Pham V, Kusche K, Vera VA, Reese F, Campbell RR, Matheos DP, Swarup V, Wood MA
NR4A2 in the medial habenula controls relapse to cocaine seeking in mice, suggesting this gene plays a key role in addiction-related behaviors. Manipulating NR4A2 disrupts the brain's reward circuitry involved in relapse, highlighting a potential target for treating substance use disorders.
- NR4A2 in the medial habenula drives relapse to cocaine use
- Blocking NR4A2 prevents reinstatement of drug-seeking behavior
- NR4A2 regulates genes linked to addiction and brain plasticity
- This pathway involves GABA and glutamate signaling networks
- Findings may inform treatments for addiction and relapse
Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia-Reperfusion Injury through NR4A2-Mediated Mitophagy.
Yu Y, Li Z, Cai Y, Guo J, Lin Y, Zhao J
Exosomes from blood vessel cells deliver a molecule called SPC that protects heart muscle cells after a heart attack by boosting a cleanup process called mitophagy through the NR4A2 pathway. This suggests SPC could be a potential treatment to reduce heart damage.
- SPC in exosomes protects heart cells after injury
- NR4A2 activation boosts mitophagy in heart cells
- Exosome delivery reduces heart damage in mice
- SPC may be a therapeutic target for heart attacks
Investigating the Effect of an Anti-Inflammatory Drug in Determining NURR1 Expression and Thus Exploring the Progression of Parkinson's Disease.
Zheng X, Zhao Z, Zhao L
Ibuprofen improved motor function and boosted NURR1 levels in early-stage Parkinson's disease in mice, but had no benefit in advanced disease. NURR1 appears to play a key role in protecting brain cells and mediating ibuprofen’s effects.
- Ibuprofen helped early Parkinson's mice recover motor function
- NURR1 levels rose with ibuprofen in early disease only
- No benefit from ibuprofen in advanced Parkinson's mice
- NURR1 has protective effects in brain cells
- Timing of treatment matters for potential benefit
Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging.
Wang Y, Li F, Mao L, Liu Y, Chen S, Liu J, Huang K, Chen Q, Wu J, Lu L, Zheng Y, Shen W, Ying T, Dai Y, Shen Y
MoS2 nanodots improve blood vessel growth in diabetic mice by activating a protective cellular process called autophagy and reducing harmful oxidative stress. This effect is driven by a specific molecular pathway involving NR4A2, which helps repair damaged blood vessels.
- MoS2 nanodots boost blood vessel formation in diabetic mice
- They activate autophagy via the cAMP/PKA-NR4A2 pathway
- They reduce oxidative stress by scavenging harmful free radicals
- The dual action enhances endothelial cell repair under high glucose
- NR4A2 is a key player in protecting blood vessels in diabetes
Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis.
Li K, Gao ZK, Guo YS, Shen XY, Han Y, Yuan M, Bi X
Preconditioning exercise in rats reduces brain damage from stroke by activating the PI3K-AKT pathway, which helps protect brain cells and improve recovery. This protective effect involves key genes like NR4A2 and others that regulate cell survival and blood vessel growth.
- Exercise before stroke reduces brain damage in rats
- The PI3K-AKT pathway is central to protection
- NR4A2 is among key genes involved in cell survival
- Exercise boosts blood vessel formation in the brain
- Reduced cell death helps preserve brain function
The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.
Solís-Barbosa MA, Santana E, Muñoz-Torres JR, Segovia-Gamboa NC, Patiño-Martínez E, Meraz-Ríos MA, Samaniego R, Sánchez-Mateos P, Sánchez-Torres C
Nurr1 is highly active in human pro-inflammatory macrophages and acts as a natural brake to reduce the production of multiple inflammatory signals, including TNF, IL-6, and reactive oxygen species. This suggests that boosting Nurr1 activity could help calm harmful inflammation in conditions like autoimmune diseases.
- Nurr1 is mainly found in pro-inflammatory human macrophages
- Activating Nurr1 reduces key inflammatory molecules
- Nurr1 limits NF-κB activity, a major driver of inflammation
- High Nurr1 levels correlate with inflammation in skin disease
- Nurr1 may be a therapeutic target to control excessive inflammation
[Rho kinase inhibitor Y27632 promotes survival of human induced pluripotent stem cells during differentiation into functional midbrain dopaminergic progenitor cells in vitro].
Li Y, Xu J, Jiang C, Chen Z, Chen Y, Ying M, Wang A, Ma C, Wang C, Guo Y, Liu C
Adding a drug called Y27632 for one day significantly improves the survival of human stem cell-derived brain cells during lab growth into dopamine-producing cells, without harming their development. This makes the process more efficient and could help in creating better cell therapies for brain disorders.
- Y27632 boosts survival of stem cell-derived brain cells
- Works during early cell separation and reattachment
- Does not interfere with final dopamine cell development
- Improves efficiency of making functional brain cells
- May support future cell-based treatments
The Synergistic Effect Study of Lipopolysaccharide (LPS) and A53T-α-Synuclein: Intranasal LPS Exposure on the A53T-α-Synuclein Transgenic Mouse Model of Parkinson's Disease.
He Q, Zhang S, Wang J, Ma T, Ma D, Wu L, Zhou M, Zhao L, Chen Y, Liu J, Chen W
Exposure to inflammation via the nose worsens Parkinson's-like symptoms in mice with a genetic form of Parkinson's disease, especially as they age. This happens because brain immune cells become overactive and suppress a key protective protein called Nurr1, leading to more nerve cell damage and worse movement problems.
- Inflammation from nasal exposure worsens Parkinson's symptoms in genetically predisposed mice
- Nurr1 protein is suppressed in brain immune cells, reducing protection
- Aging and genetic mutation together increase brain inflammation and nerve cell loss
- Symptoms include smell loss, movement issues, and dopamine decline
- This suggests inflammation may trigger or speed up Parkinson's in vulnerable individuals
Oxidized low-density lipoproteins impair the pro-atherosclerotic effect of granulocyte-macrophage-colony-stimulating factor-producing T helper cells on macrophages.
Xiong X, Yan Z, Yan L, Yang X, Li D, Lin G
Oxidized LDL reduces the ability of a specific type of immune cell (ThGM cells) to promote inflammation and foam cell formation in macrophages, which are key drivers of atherosclerosis. This effect involves the NR4A1 and NR4A2 nuclear receptors, suggesting a potential link to NR4A2-related syndromes.
- OxLDL suppresses ThGM cell activity in atherosclerosis
- NR4A1 and NR4A2 are involved in this suppression
- ThGM cells promote macrophage inflammation and foam cell formation
- OxLDL reduces pro-atherosclerotic effects of ThGM cells
- NR4A2 may play a role in immune regulation in vascular disease
Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.
Hill MD, Gill SS, Le-Niculescu H, MacKie O, Bhagar R, Roseberry K, Murray OK, Dainton HD, Wolf SK, Shekhar A, Kurian SM, Niculescu AB
Blood gene expression levels of specific genes, including NR4A2, can predict hallucinations, delusions, and future hospitalizations in people with psychotic disorders. These biomarkers point to key brain pathways and suggest existing drugs like clozapine, lithium, and omega-3s may be especially helpful for some patients.
- NR4A2 is a top blood biomarker for delusions in psychosis
- Gene patterns predict hospitalization risk and treatment response
- Existing drugs like clozapine and lithium may be prioritized based on biomarker profiles
- Personalized lab reports could guide treatment decisions
- Biomarkers reflect brain pathways involved in psychosis
Structural characterization of the DNA binding mechanism of retinoic acid-related orphan receptor gamma.
Jiang L, Liu X, Liang X, Dai S, Wei H, Guo M, Chen Z, Xiao D, Chen Y
This study reveals how RORγ, a related nuclear receptor, binds DNA as a dimer, but NR4A2 binds the same DNA sequence as a monomer, suggesting different regulatory mechanisms. The findings help explain how NR4A2 might function differently from other similar proteins in gene control.
- NR4A2 binds DNA as a monomer, unlike RORγ which binds as a dimer
- The DNA sequence DR2 is recognized differently by NR4A2 and RORγ
- NR4A2's unique binding mode may affect how it regulates genes
- This insight helps clarify NR4A2's role in gene expression
Pathological features and molecular signatures of early olfactory dysfunction in 3xTg-AD model mice.
Yu H, Wang F, Jia D, Bi S, Gong J, Wu JJ, Mao Y, Chen J, Chai GS
Olfactory problems in early Alzheimer's disease are linked to buildup of toxic proteins in the smell-processing brain area, triggering inflammation and reduced neuron activity. The genes Nr4a2 and FosB are downregulated, suggesting they could be targets for treating early smell loss.
- Early Alzheimer's smell loss involves protein buildup in the olfactory bulb
- Neuroinflammation and reduced neuron activity occur before memory issues
- Nr4a2 and FosB levels drop, linking them to smell dysfunction
- Axonal transport problems contribute to olfactory decline
- Targeting Nr4a2 may help treat early smell loss in Alzheimer's
Nr4a2 blocks oAβ-mediated synaptic plasticity dysfunction and ameliorates spatial memory deficits in the APP Sw,Ind mouse.
Català-Solsona J, Lutzu S, Lituma PJ, Fábregas-Ordoñez C, Siedlecki D, Giménez-Llort L, Miñano-Molina AJ, Saura CA, Castillo PE, Rodriguez-Álvarez J
Reducing amyloid-beta oligomers in Alzheimer's disease harms the function of a key brain protein called Nr4a2, which is needed for learning and memory. Boosting Nr4a2 activity protects brain connections and improves memory in mouse models of Alzheimer's, suggesting it could be a treatment target.
- Amyloid-beta blocks Nr4a2, harming brain function
- Nr4a2 levels drop in early Alzheimer's brains
- Activating Nr4a2 protects memory and brain connections
- Nr4a2 may be a treatment target for early Alzheimer's
PROKR1-CREB-NR4A2 axis for oxidative muscle fiber specification and improvement of metabolic function.
Mok J, Park JH, Yeom SC, Park J
Activating the PROKR1-CREB-NR4A2 pathway increases oxidative muscle fibers and improves metabolic function in muscle cells, which may help treat metabolic and muscular disorders. This pathway boosts mitochondrial health and energy use, and its disruption leads to poor muscle and metabolic performance.
- PROKR1 activates NR4A2 to boost oxidative muscle fibers
- NR4A2 enhances mitochondrial function and metabolism
- PROKR1 loss causes metabolic and muscle defects
- Restoring PROKR1 improves muscle and metabolic health
- This pathway offers a new target for treating muscle-metabolic diseases
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, PGC-SUD Epigenetics Working Group, Hancock DB, Montalvo-Ortiz J, Corradin O, Logan RW, Walss-Bass C, Maher BS, Johnson EO
This study found that opioid overdose death is linked to changes in the activity of 335 genes in the brain's prefrontal cortex, including NR4A2, which is involved in brain development and function and may play a role in neurological disorders. The changes affect key brain signaling pathways related to neuron flexibility and stress response.
- NR4A2 is among genes altered in opioid overdose death
- Changes affect brain pathways tied to neuron flexibility and stress
- Findings may help understand brain impacts of opioid use
- Large study increases confidence in gene findings
Gene architecture is a determinant of the transcriptional response to bulky DNA damages.
Merav M, Bitensky EM, Heilbrun EE, Hacohen T, Kirshenbaum A, Golan-Berman H, Cohen Y, Adar S
Certain genes, including NR4A2, stay active or increase in expression when DNA is damaged by agents like UV, cisplatin, or cigarette smoke components. Gene features like shorter length, higher GC content, and more exons help protect genes from being shut down during DNA damage. This suggests that the structure of genes influences how well they survive and respond to damage.
- NR4A2 is upregulated after DNA damage, suggesting a role in the damage response
- Shorter genes with more exons are better protected from transcription shutdown
- Gene structure determines how genes respond to DNA damage
- Different DNA-damaging agents trigger distinct transcriptional responses
- This may explain why some genes remain active during stress
Reprogramming astrocytes into dopaminergic neurons to restore motor dysfunction in Parkinson's disease model rats.
Liu C, Ying M, Wang A, Liu Y, Chen Y, Ye W, Wen H, Ma C, Liu C, Guo Y
Reprogramming star-shaped brain cells into dopamine-producing neurons using two key genes, NURR1 and ASCL1, successfully restored movement in rats with Parkinson's-like symptoms. The new neurons survived, integrated into brain circuits, and improved motor function after transplantation.
- NURR1 and ASCL1 genes reprogrammed brain cells into dopamine neurons
- Transplanted neurons survived and improved movement in Parkinson's rats
- New neurons expressed key markers of dopamine-producing cells
- Results suggest a potential therapy for Parkinson's disease
- Uses the patient's own brain cells, avoiding immune rejection
Investigating In silico and In vitro Therapeutic Potential of Diosmetin as the Anti-Parkinson Agent.
Varshney KK, Gupta JK, Srivastava R
Diosmetin shows strong potential to interact with key receptors involved in Parkinson's disease, including NURR1, and may help reduce oxidative stress, a major driver of brain cell damage in PD.
- Diosmetin binds strongly to NURR1, a critical gene in dopamine neuron health.
- It targets multiple pathways linked to Parkinson's, including oxidative stress and inflammation.
- The compound effectively neutralizes harmful free radicals like nitric oxide and hypochlorous acid.
- These findings suggest diosmetin could protect brain cells in Parkinson's disease.
- Results come from computer modeling and lab tests, not human trials yet.
Structural Perspective of NR4A Nuclear Receptor Family and Their Potential Endogenous Ligands.
Hashida R, Kawabata T
NR4A2, a gene linked to neurological disorders, can be activated by natural compounds called prostaglandin A1 and A2, which bind directly to the protein and may protect brain cells. These findings come from detailed structural studies and animal models of Parkinson’s disease, suggesting potential therapeutic pathways.
- NR4A2 is activated by prostaglandin A1 and A2
- These compounds bind directly to NR4A2's structure
- They show neuroprotective effects in Parkinson’s models
- Structural insights may guide future treatments
- NR4A2 activation could help in NR4A2-related syndromes