Pink1 Regulates Tyrosine Hydroxylase Expression and Dopamine Synthesis.
Lu L, Jia H, Gao G, Duan C, Ren J, Li Y, Yang H
PINK1 helps control dopamine production by activating a key protein that turns on the gene for tyrosine hydroxylase, the enzyme that makes dopamine. Without PINK1, dopamine levels drop even if dopamine-making cells remain intact.
- PINK1 boosts dopamine by activating tyrosine hydroxylase
- PINK1 loss reduces dopamine without killing neurons
- PINK1 helps a critical protein enter the nucleus to turn on dopamine genes
- This pathway may be relevant for Parkinson’s and dopamine-related disorders
Neuroprotective effect of olfactory ensheathing cells co-transfected with Nurr1 and Ngn2 in both in vitro and in vivo models of Parkinson's disease.
Liu Q, Qin Q, Sun H, Zhong D, An R, Tian Y, Chen H, Jin J, Wang H, Li G
Olfactory ensheathing cells engineered to produce Nurr1 and Ngn2 proteins protect dopamine neurons in models of Parkinson's disease by reducing oxidative stress and cell death, likely through activation of a key brain survival pathway.
- Engineered cells protect dopamine neurons in lab and animal models
- Reduced oxidative stress and cell death in Parkinson's models
- Effect depends on activation of the TrkB brain survival pathway
- Improved movement symptoms in Parkinson's rats
- Suggests a potential therapy for neurodegenerative diseases
CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters.
Parra-Damas A, Rubió-Ferrarons L, Shen J, Saura CA
Neuronal activity triggers CRTC1 to bind specifically to genes with CRE/TATA promoter sequences, turning on key brain-related genes like NR4A2. This process is essential for activity-dependent gene expression in neurons.
- CRTC1 binds only to CRE/TATA promoters during brain activity
- NR4A2 is among genes activated this way
- CRTC1 moves to the nucleus only when neurons fire
- This mechanism controls critical brain function genes
- Disruption may affect neurodevelopment and behavior
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
Pregnant and nursing mice exposed to glyphosate had altered microRNA levels in their offspring's prefrontal cortex, disrupting key brain development pathways like Wnt and Notch. These changes affected genes such as Nr4a2, which is linked to neurodevelopmental disorders, suggesting glyphosate may interfere with brain development in ways relevant to conditions like NR4A2-related syndrome.
- Glyphosate exposure disrupts brain development pathways in mouse offspring
- Nr4a2, a gene tied to NR4A2-related syndrome, was downregulated
- Wnt and Notch signaling—critical for brain development—were impaired
- Altered microRNAs may contribute to neurodevelopmental issues
- Findings suggest environmental toxins could worsen or mimic NR4A2 syndrome
Cografting astrocytes improves cell therapeutic outcomes in a Parkinson's disease model.
Song JJ, Oh SM, Kwon OC, Wulansari N, Lee HS, Chang MY, Lee E, Sun W, Lee SE, Chang S, An H, Lee CJ, Lee SH
Cotransplanting astrocytes, especially midbrain-derived ones, significantly improves the survival and function of neural progenitor cells in a Parkinson's disease model, leading to long-term dopamine neuron recovery. Engineering these astrocytes with Nurr1 and Foxa2 boosts their ability to support neuron growth and repair.
- Astrocytes enhance stem cell therapy in Parkinson's models
- Midbrain-derived astrocytes work best for dopamine neuron recovery
- Adding Nurr1 and Foxa2 makes astrocytes more protective
- Benefits last at least 6 months after transplant
- This approach could improve cell therapies for brain disorders
Creating a graft-friendly environment for stem cells in diseased brains.
Tsai RY
Engineered astrocytes that produce the Nurr1 and Foxa2 proteins create a supportive environment in the brain, helping transplanted stem cells survive, mature, and improve symptoms in a rat model of Parkinson’s disease. This approach could lead to better stem cell therapies for neurodegenerative conditions like NR4A2-related syndrome.
- Engineered astrocytes boost stem cell survival and function
- Nurr1 and Foxa2 are key for neuron development and repair
- This strategy improves outcomes in Parkinson’s disease models
- May inform future treatments for NR4A2-related disorders
- Supports the idea of modifying brain environment for therapy
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
Activating liver X receptors (LXR) with a drug boosts the efficiency and speed at which rat bone marrow stem cells turn into dopamine-producing nerve cells, a key step toward potential cell therapies for Parkinson’s disease. This effect depends on combining the LXR drug with growth factors, not using the drug alone.
- LXR activation improves stem cell conversion to dopamine neurons
- Combining LXR drug with growth factors increases efficiency to 87%
- LXR boosts key genes needed for dopamine neuron development
- LXR treatment shortens the time needed for differentiation
- LXR may be a target for future Parkinson’s therapies
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 identifies eight new transcription factors, including NR4A2, that can specifically remove DNA methylation at targeted gene sites, a process linked to gene activation during development. These factors preferentially act on highly methylated regions and often affect genes related to their known biological roles.
- NR4A2 is one of eight newly identified factors that drive site-specific DNA demethylation
- These factors target highly methylated CpG sites and cause local demethylation
- Demethylation aligns with the biological functions of each transcription factor
- The findings suggest a mechanism by which gene expression is precisely regulated during development
- The screening method can help discover other epigenetic regulators with therapeutic potential
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
Blocking miR-145-5p boosts Nurr1 levels, reduces brain inflammation, and protects neurons after stroke in rats, suggesting a potential treatment strategy for brain injury involving Nurr1 dysfunction.
- miR-145-5p suppresses Nurr1 in stroke
- Nurr1 reduces harmful brain inflammation
- Blocking miR-145-5p protects brain tissue
- Anti-miR-145-5p improves recovery after stroke
- This pathway may be targeted for brain injury treatment
Long 3'UTR of Nurr1 mRNAs is targeted by miRNAs in mesencephalic dopamine neurons.
Pereira LA, Munita R, González MP, Andrés ME
A specific form of the Nurr1 mRNA, with a long 3'UTR, is regulated by certain microRNAs in dopamine neurons. This regulation fine-tunes Nurr1 protein levels, which are critical for the development and survival of these neurons. Disruptions in this process may contribute to neurological conditions linked to Nurr1 dysfunction.
- Long 3'UTR Nurr1 mRNA is targeted by miR-93, miR-204, and miR-302d
- These miRNAs reduce Nurr1 protein levels in dopamine neurons
- This regulation helps fine-tune Nurr1, essential for neuron health
- The long 3'UTR variant is present in the brain region affected in NR4A2 syndrome
- Potential for future therapies targeting miRNA-Nurr1 interactions
Tcf12 Is Involved in Early Cell-Fate Determination and Subset Specification of Midbrain Dopamine Neurons.
Mesman S, Smidt MP
Tcf12 is a key gene that helps control the early development and specialization of midbrain dopamine neurons, which are affected in NR4A2-related syndrome. It influences the formation of specific neuron subtypes and their proper positioning, with disruptions leading to lasting changes in neuron populations.
- Tcf12 guides early fate of dopamine neuron precursors
- Tcf12 loss disrupts neuron subtype specification
- Delayed development of specific dopamine neuron subsets
- Tcf12 affects both early and late stages of neuron maturation
- Findings may inform therapies targeting dopamine neuron development
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 study developed a new statistical method to analyze protein changes over time in cells, successfully identifying key signaling proteins including NR4A2 in response to a cancer drug. The method improves detection of biologically meaningful changes in protein activity, especially in complex, variable data.
- New algorithm detects protein changes over time more reliably
- Identified NR4A2 as a responsive protein in signaling pathways
- Method improves detection of drug targets in noisy data
- Could help find new treatment targets in resistant cancers
Effect on the dopaminergic metabolism induced by oral exposure to simazine during the prepubertal period in rats.
Li X, Yu J, Wu Y, Li B
Exposure to the herbicide simazine during early development reduces dopamine levels in the brain of rats by disrupting dopamine production, transport, and breakdown. This occurs through reduced levels of key proteins like Nurr1, DAT, and VMAT2, and altered activity of enzymes involved in dopamine metabolism.
- Simazine lowers dopamine in the brain during development
- It reduces Nurr1, DAT, and VMAT2 proteins critical for dopamine function
- Enzymes for dopamine synthesis and breakdown are disrupted
- These changes may lead to long-term brain function issues
- Findings suggest environmental toxins can harm dopamine systems
Effect of Wnt1 and Wnt5a on the development of dopaminergic neurons, and toxicity induced by combined exposure to paraquat and maneb during gestation and lactation.
Ma J, Huang C, Ma K, Wu YP, Li BX, Sun Y
Exposure to the pesticides paraquat and maneb during pregnancy and nursing reduces key proteins needed for dopamine neuron development and function in rat offspring, including Nurr1, which is the human gene mutated in NR4A2-related syndrome. This suggests environmental toxins may worsen the neurological impact of NR4A2/NURR1 deficiency.
- Pesticide exposure harms dopamine neuron development
- Nurr1, Wnt1, and TH levels drop in exposed offspring
- Wnt5a increases, possibly disrupting neuron maturation
- Findings mirror issues seen in NR4A2-related syndrome
- Environmental toxins may worsen NR4A2-related symptoms
Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson's disease. An integrated strategy for management.
Phillipson OT
This review proposes a combination of nutrients—R-lipoic acid, acetyl-L-carnitine, ubiquinol, melatonin, and vitamin D3—to target multiple interconnected problems in Parkinson's disease, including mitochondrial dysfunction, oxidative stress, and alpha-synuclein buildup. These nutrients may support brain cell survival by boosting NR4A2, GDNF, BDNF, and autophagy, while also improving circadian rhythms and metabolism.
- Nutrients may slow Parkinson's progression by supporting mitochondria and reducing stress
- NR4A2, a key brain survival gene, may be boosted by these nutrients
- Combination therapy targets alpha-synuclein buildup and supports cellular cleanup
- Melatonin and vitamin D3 help regulate sleep and circadian rhythms
- AMPK and mTOR pathways are influenced to improve cellular energy and repair
Permethrin pesticide induces NURR1 up-regulation in dopaminergic cell line: Is the pro-oxidant effect involved in toxicant-neuronal damage?
Bordoni L, Fedeli D, Nasuti C, Capitani M, Fiorini D, Gabbianelli R
Permethrin pesticide increases NURR1 levels in dopamine-producing cells, likely due to oxidative stress, and antioxidants like electrolyzed reduced water can reduce this increase. This suggests pesticide exposure may trigger a protective response in brain cells.
- Permethrin raises NURR1 levels in dopamine cells
- Oxidative stress may drive NURR1 increase
- Antioxidants reduce NURR1 up-regulation
- Electrolyzed reduced water shows strong effect
- Findings may inform protection strategies
Differentiation of mesenchymal stem cells -derived trabecular meshwork into dopaminergic neuron-like cells on nanofibrous scaffolds.
Jamali S, Mostafavi H, Barati G, Eskandari M, Nadri S
Human stem cells from the eye's trabecular meshwork can be turned into dopamine-producing cells on a special nanofiber scaffold, suggesting a potential new source for cell therapy in Parkinson's disease.
- Stem cells from eye tissue can become dopamine-making cells
- A nanofiber scaffold supports this transformation
- Cells express key markers for dopamine neurons
- This approach may help treat Parkinson's disease
- The scaffold could carry cells to the brain
The ROS/NF-κB/NR4A2 pathway is involved in H2O2 induced apoptosis of resident cardiac stem cells via autophagy.
Shi X, Li W, Liu H, Yin D, Zhao J
High levels of hydrogen peroxide, mimicking the stressful environment after a heart attack, trigger cell death in heart stem cells through a chain reaction involving ROS, NF-κB, and the NR4A2 protein. Blocking NR4A2 or the pathway that activates it reduces cell death, suggesting a potential way to improve stem cell survival in heart repair therapies.
- NR4A2 increases under heart stress and drives stem cell death
- ROS and NF-κB activate NR4A2 in heart stem cells
- Blocking NR4A2 protects heart stem cells from damage
- This pathway could be targeted to improve heart cell therapy
- Findings may help boost stem cell survival after heart attacks
Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons.
Pereira M, Birtele M, Shrigley S, Benitez JA, Hedlund E, Parmar M, Ottosson DR
Reprogramming brain glia into neurons can generate fast-spiking, parvalbumin-containing interneurons, which are crucial for brain circuit function and often impaired in neurodevelopmental disorders. This approach works across different brain regions and gene combinations, suggesting a promising path for repairing brain circuits in conditions like NR4A2-related syndrome.
- Reprogrammed neurons resemble parvalbumin interneurons
- Works in multiple brain regions and with different gene sets
- Generated neurons integrate into brain circuits
- Potential for repairing circuit dysfunction in neurodevelopmental disorders
NR4A proteins and neutrophil lifespan.
Allen LH
NR4A2 and NR4A3 proteins control how long neutrophils live in the body, and their function depends on cAMP and PKA signaling. This insight may help develop treatments for immune disorders linked to neutrophil imbalance.
- NR4A2 and NR4A3 regulate neutrophil lifespan
- They work through cAMP and PKA pathways
- This affects immune system balance
- Potential for new therapies targeting neutrophil survival
Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis.
Choi YJ, Song I, Jin Y, Jin HS, Ji HM, Jeong SY, Won YY, Chung YS
The study found that genes in bone stem cells differ in women with osteoporosis, and the NR4A family, especially NR4A2, is linked to both bone loss and fat accumulation. Higher levels of NR4A2 mRNA were seen in obese individuals, suggesting a role in metabolic and bone disorders.
- NR4A2 levels are elevated in obesity
- NR4A family links bone and fat cell development
- Changes in stem cells may drive osteoporosis
- NR4A2 could be a shared factor in bone and fat disorders
The Non-Survival Effects of Glial Cell Line-Derived Neurotrophic Factor on Neural Cells.
Cortés D, Carballo-Molina OA, Castellanos-Montiel MJ, Velasco I
GDNF supports more than just neuron survival—it helps neural cells develop, grow, and function properly, including promoting dopamine-producing neuron identity and aiding nerve repair. This broad role suggests GDNF could be useful in treating neurological conditions involving nerve damage or dysfunction.
- GDNF helps neurons develop and mature, not just survive
- It boosts dopamine neuron identity and function
- GDNF supports nerve repair and connection formation
- It influences motor neuron growth and nerve junctions
- GDNF may help treat neurological disorders beyond survival
Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool.
Kouwenhoven WM, von Oerthel L, Smidt MP
Pitx3 and En1 are critical transcription factors that control the number and identity of dopamine-producing brain cells. Without both proteins, these neurons fail to develop properly and lose their regional specialization along the brain's rostral-caudal axis.
- Pitx3 and En1 jointly regulate dopamine neuron size and identity
- Loss of both proteins leads to few, underdeveloped dopamine neurons
- Pitx3 and En1 are needed for correct regional programming
- Cck expression depends on En1; Ahd2 requires both factors
- These genes maintain dopamine neuron survival and specialization
Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure.
Suzuki D, Saito-Hakoda A, Ito R, Shimizu K, Parvin R, Shimada H, Noro E, Suzuki S, Fujiwara I, Kagechika H, Rainey WE, Kure S, Ito S, Yokoyama A, Sugawara A
The drug PA024, which activates RXR receptors, reduces the production of aldosterone—a hormone that raises blood pressure—by suppressing key genes involved in its synthesis. This effect occurs through the inhibition of NURR1, a transcription factor linked to NR4A2, and lowers blood pressure in a mouse model of hypertension.
- PA024 reduces aldosterone production by blocking CYP11B2 gene activity
- It works by lowering NURR1 levels, which regulates aldosterone synthesis
- PA024 lowers blood pressure in a hypertensive mouse model
- Combining PA024 with pioglitazone boosts its effect
- RXR activation may be a new way to treat hormone-related high blood pressure
Acute and chronic effects of exercise on mRNA expression in the skeletal muscle of two mouse models of peripheral artery disease.
Nagase H, Yao S, Ikeda S
Exercise changes gene activity in the leg muscles of mice with poor blood flow, a condition similar to human peripheral artery disease. These changes involve genes linked to energy production, muscle repair, and tissue structure, with some effects seen immediately and others after repeated exercise.
- Exercise boosts key genes involved in energy and muscle health in diseased muscles
- Some muscle repair genes increase in sedentary mice with poor blood flow
- Exercise reduces abnormal increases in certain repair and structural genes
- Gene changes differ between normal and diabetic mice, suggesting metabolic influence
- Findings may help explain how exercise improves walking in people with PAD
The FOXP2-Driven Network in Developmental Disorders and Neurodegeneration.
Oswald F, Klöble P, Ruland A, Rosenkranz D, Hinz B, Butter F, Ramljak S, Zechner U, Herlyn H
This study identifies genes regulated by FOXP2, a key gene involved in brain development and speech, and links them to multiple neurodevelopmental and neurodegenerative disorders. The findings suggest that FOXP2 influences critical brain processes like neuron formation, signaling, and connectivity, with direct relevance to conditions like autism, schizophrenia, and Parkinson’s disease.
- FOXP2 regulates genes tied to brain development and function
- Links found to autism, schizophrenia, Parkinson’s, and other brain disorders
- New pathways involving neuron growth and signaling identified
- NURR1 is among proteins connected to FOXP2 network
- Findings may help explain molecular causes of developmental brain conditions
Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.
Dela Peña I, Dela Peña IJ, de la Peña JB, Kim HJ, Shin CY, Han DH, Kim BN, Ryu JH, Cheong JH
The study found that rats with impulsive behavior share changes in brain gene activity in the prefrontal cortex, including the NR4A2 gene, which is also affected by ADHD medications methylphenidate and atomoxetine. These gene changes are linked to brain function areas involved in impulse control and may help predict how well a child responds to certain ADHD drugs.
- NR4A2 gene is altered in impulsive rats and responds to ADHD meds
- Brain gene changes may predict response to methylphenidate or atomoxetine
- Findings could lead to better treatments for impulsivity in NR4A2-related syndrome
- Gene activity changes are linked to brain circuits controlling decision-making
Ligand Dependent Switch from RXR Homo- to RXR-NURR1 Heterodimerization.
Scheepstra M, Andrei SA, de Vries RMJM, Meijer FA, Ma JN, Burstein ES, Olsson R, Ottmann C, Milroy LG, Brunsveld L
This study identifies new molecules that can switch RXR proteins from pairing with themselves to pairing with NURR1, a key protein for dopamine neuron health. These molecules stabilize the RXR-NURR1 partnership, which may help protect or restore dopamine neurons in conditions like NR4A2-related syndrome.
- New molecules force RXR to pair with NURR1 instead of itself
- This pairing may support dopamine neuron survival
- The design could lead to treatments targeting NR4A2-related disorders
- Changes in protein shape explain how the molecules work
Valproate increases dopamine transporter expression through histone acetylation and enhanced promoter binding of Nurr1.
Green AL, Zhan L, Eid A, Zarbl H, Guo GL, Richardson JR
Valproate increases dopamine transporter levels by modifying chromatin structure and boosting the activity of Nurr1, a key protein involved in dopamine neuron development. This suggests a potential mechanism by which valproate could influence dopamine signaling, which may be relevant for conditions involving dopamine dysfunction.
- Valproate boosts dopamine transporter levels in cells
- It works by increasing histone acetylation at the DAT gene
- Nurr1 binding to the DAT gene is enhanced
- This mechanism may affect dopamine signaling
- Findings could inform treatments for dopamine-related disorders
cDNA microarray analysis identifies NR4A2 as a novel molecule involved in the pathogenesis of Sjögren's syndrome.
Takahashi H, Tsuboi H, Asashima H, Hirota T, Kondo Y, Moriyama M, Matsumoto I, Nakamura S, Sumida T
NR4A2 is overactive in immune cells of people with Sjögren's syndrome, driving harmful immune responses that contribute to the disease. Blocking NR4A2's movement into cell nuclei reduces the activity of key immune cells involved in inflammation.
- NR4A2 is abnormally high in immune cells of Sjögren's patients
- NR4A2 promotes inflammatory Th17 cells in Sjögren's
- Blocking NR4A2 nuclear entry reduces harmful immune activity
- NR4A2 may be a target for new Sjögren's treatments
- Findings are based on human tissue and immune cells
Efficient Generation of Dopamine Neurons by Synthetic Transcription Factor mRNAs.
Kim SM, Lim MS, Lee EH, Jung SJ, Chung HY, Kim CH, Park CH
This study shows that mRNA delivery of key genes Nurr1 and FoxA2 can efficiently turn precursor cells into functional dopamine neurons without causing DNA damage, offering a safer method for generating cells that could treat Parkinson's disease.
- mRNA delivery avoids DNA damage from viral or plasmid methods
- Nurr1 and FoxA2 mRNAs alone can create dopamine neurons
- Adding db-cAMP and timing adjustments boosts neuron production
- Generated neurons show proper electrical and biochemical traits
- Method is safe and suitable for clinical cell therapy development
NURR1 Downregulation Favors Osteoblastic Differentiation of MSCs.
Di Benedetto A, Posa F, Carbone C, Cantore S, Brunetti G, Centonze M, Grano M, Lo Muzio L, Cavalcanti-Adam EA, Mori G
Reducing NURR1 levels in dental stem cells strongly promotes their development into bone-forming cells, suggesting that NURR1 normally acts as a brake on bone formation. This finding may help guide future therapies aimed at enhancing bone repair in NR4A2-related conditions.
- Lowering NURR1 boosts bone cell formation in stem cells
- NURR1 normally suppresses bone development
- This effect was seen in dental stem cells
- Could inform treatments for bone-related issues in NR4A2 syndrome
Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson's disease.
Gnanasegaran N, Govindasamy V, Mani V, Abu Kasim NH
Dental pulp stem cells (DPSCs) reduce inflammation and protect dopamine-producing neurons in a lab model of Parkinson's disease, even in harsh conditions. They lower harmful molecules like reactive oxygen species and nitric oxide, and maintain expression of key brain-related genes, suggesting potential for cell therapy in Parkinson's.
- DPSCs reduce harmful inflammation in Parkinson's models
- They protect dopamine neurons from damage
- DPSCs maintain brain-related gene expression
- They may support cell therapy for Parkinson's
- Results suggest therapeutic potential in neurodegeneration
Parkinsonian features in aging GFAP.HMOX1 transgenic mice overexpressing human HO-1 in the astroglial compartment.
Song W, Cressatti M, Zukor H, Liberman A, Galindez C, Schipper HM
Overexpressing the stress protein HO-1 in astrocytes of aging mice leads to Parkinson’s-like brain changes, including dopamine loss, movement problems, and brain cell damage, suggesting that glial stress responses may trigger Parkinsonism in later life.
- HO-1 overexpression in astrocytes causes Parkinson’s-like symptoms in aging mice
- Dopamine systems deteriorate, with reduced key proteins and increased toxic proteins
- Brain iron buildup, oxidative stress, and mitochondrial damage are observed
- Timing of glial stress response may determine whether brain disorders are developmental or degenerative
- Reducing glial HO-1 activity might protect against Parkinsonism and similar disorders
NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival.
Prince LR, Prosseda SD, Higgins K, Carlring J, Prestwich EC, Ogryzko NV, Rahman A, Basran A, Falciani F, Taylor P, Renshaw SA, Whyte MKB, Sabroe I
NR4A2 and NR4A3 are key genes that control neutrophil survival and number, activated by signals that extend neutrophil lifespan. These genes are turned on by PKA signaling, which is involved in inflammation and immune responses. Reducing NR4A2 or NR4A3 leads to fewer neutrophils, showing their essential role in immune cell maintenance.
- NR4A2 and NR4A3 boost neutrophil survival
- They are activated by PKA signaling during inflammation
- Lowering these genes reduces neutrophil numbers
- This pathway affects immune cell homeostasis
- May influence chronic inflammation and immune disorders