Beta-adrenergic signaling regulates NR4A nuclear receptor and metabolic gene expression in multiple tissues.
Myers SA, Eriksson N, Burow R, Wang SC, Muscat GE
Beta-adrenergic signaling strongly activates NR4A2 and other NR4A genes in multiple tissues, including the liver, heart, and fat, and this activation is linked to changes in genes that control metabolism. This suggests that stress or adrenaline-like signals may influence NR4A2 activity in ways that affect energy use and metabolic health.
- Beta-adrenergic signals turn on NR4A2 in many organs
- This occurs rapidly, within hours of stimulation
- NR4A2 activation is tied to changes in metabolic genes
- Liver, heart, and fat tissue all respond to this signaling
- May affect how the body uses energy and handles metabolism
Generation of dopaminergic neurons from human fetal mesencephalic progenitors after co-culture with striatal-conditioned media and exposure to lowered oxygen.
Liu S, Tian Z, Yin F, Zhao Q, Fan M
This study shows that combining striatal-conditioned media and low oxygen levels helps human fetal brain cells develop into mature dopamine-producing neurons, which could inform future treatments for NR4A2-related disorders.
- Striatal-conditioned media boosts dopamine neuron development
- Low oxygen (3-5%) improves neuron branching and maturity
- Combined conditions increase dopamine release and key gene expression
- Nurr1 and other maturation genes are activated under low oxygen
- Findings may guide therapies for dopamine-related neurological conditions
Mechanisms of angiotensin II-mediated regulation of aldosterone synthase expression in H295R human adrenocortical and rat adrenal glomerulosa cells.
Szekeres M, Turu G, Orient A, Szalai B, Süpeki K, Cserzo M, Várnai P, Hunyady L
This study compares how angiotensin II controls aldosterone production in human and rat adrenal cells, finding that the NR4A2 gene (which is linked to your child’s syndrome) is rapidly activated by angiotensin II in both cell types, with different signaling pathways involved. In human cells, the ERK pathway and a non-classical angiotensin II receptor mechanism contribute to NR4A2 and aldosterone synthase activation, suggesting potential therapeutic targets.
- NR4A2 is rapidly turned on by angiotensin II in human adrenal cells
- ERK signaling helps control NR4A2 and aldosterone production in human cells
- A non-classical angiotensin II receptor may also play a role in human cells
- Signaling differs between human and rat adrenal cells
- These findings may inform treatments targeting aldosterone overproduction
Nur(R1)turing a notion on the etiopathogenesis of Parkinson's disease.
Federoff HJ
Nurr1, a key protein for developing dopamine neurons, may play a role in why these neurons are vulnerable in Parkinson's disease. The study finds that Nurr1 controls a growth factor important for dopamine neuron survival and interacts with another protein that regulates its activity, suggesting Parkinson's could stem from early developmental issues rather than just aging.
- Nurr1 helps form dopamine neurons during development
- Nurr1 controls VIP, a factor that supports dopamine neuron survival
- A new protein, NuIP, regulates Nurr1's activity
- This supports the idea that Parkinson's may begin early in life
- Nurr1 could be a target for future treatments
Orphan nuclear receptor Nurr1 induces neuron differentiation from embryonic cortical precursor cells via an extrinsic paracrine mechanism.
Bae EJ, Lee HS, Park CH, Lee SH
Nurr1 promotes the development of neurons from brain precursor cells by sending signals to nearby cells, rather than acting directly. This process involves specific diffusible factors and downstream genes that drive neuron formation.
- Nurr1 drives neuron formation from brain precursor cells
- It works by sending signals to neighboring cells
- Specific factors and genes control this process
- Findings may help guide future therapies for NR4A2-related disorders
A Nurr1 pathway for neuroprotection.
Bensinger SJ, Tontonoz P
Nurr1 protects dopamine-producing brain cells by reducing harmful inflammation in support cells in the brain, which may help prevent Parkinson's disease.
- Nurr1 reduces brain inflammation that harms dopamine neurons
- It works by calming immune-like brain cells (astrocytes and microglia)
- This pathway could be targeted to protect neurons in Parkinson's
- Findings are based on mouse models but relevant to human Nurr1 function
A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death.
Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK
Nurr1 helps protect dopamine-producing brain cells by calming harmful inflammation in support cells called microglia and astrocytes. When Nurr1 is low, these support cells overreact and release toxic substances that kill dopamine neurons. This process may explain why Nurr1 mutations increase Parkinson’s risk.
- Nurr1 reduces harmful brain inflammation in support cells
- Low Nurr1 leads to toxic signals that kill dopamine neurons
- Nurr1 blocks inflammation by removing a key inflammatory protein
- This pathway may protect against Parkinson’s disease
- Targeting this pathway could lead to new treatments
Differentiation of dopaminergic neurons from human embryonic stem cells: modulation of differentiation by FGF-20.
Shimada H, Yoshimura N, Tsuji A, Kunisada T
FGF-20 boosts the development of dopamine-producing neurons from human stem cells, enhancing key genes linked to Parkinson's disease and offering a path toward better cell therapies. This process works without needing support cells, making it more efficient and scalable.
- FGF-20 improves dopamine neuron formation from stem cells
- Increases critical genes like NURR1 and PITX3
- Works without support cells, simplifying the process
- Relevant for future Parkinson’s cell transplants
- May inform treatments for NR4A2-related disorders
Expression of the orphan nuclear receptor NR4A in a putative adenohypophyseal homologue of amphioxus.
Candiani S, Moronti L, Pestarino M
The study identifies a single NR4A gene in amphioxus, a simple chordate, that is active only in a structure similar to the pituitary gland. This suggests the NR4A family may have ancient origins in regulating endocrine development.
- Amphioxus has one NR4A gene active in a pituitary-like tissue
- NR4A genes may have early evolutionary roles in hormone-producing cells
- Findings hint at conserved functions in pituitary development
- No direct link to human NR4A2-related syndrome yet
Differences between subacute and chronic MPTP mice models: investigation of dopaminergic neuronal degeneration and alpha-synuclein inclusions.
Gibrat C, Saint-Pierre M, Bousquet M, Lévesque D, Rouillard C, Cicchetti F
The 14-day chronic MPTP infusion in mice best mimics early Parkinson's disease by causing dopaminergic neuron loss and forming alpha-synuclein inclusions, which are key features of the disease. This model may help test treatments for NR4A2-related disorders that involve similar neurodegeneration and protein aggregation.
- 14-day MPTP infusion causes alpha-synuclein inclusions in dopamine neurons
- This model matches early Parkinson's disease pathology better than others
- Dopamine neuron loss and Nurr1 reduction were observed
- Chronic infusion method matters for disease-like outcomes
- May inform therapies targeting neurodegeneration and protein clumping
Left ventricular global transcriptional profiling in human end-stage dilated cardiomyopathy.
Colak D, Kaya N, Al-Zahrani J, Al Bakheet A, Muiya P, Andres E, Quackenbush J, Dzimiri N
This study found that genes involved in energy production, cell death, and mitochondrial function are significantly altered in heart failure patients with dilated cardiomyopathy. NR4A2, a gene linked to neurological disorders, was notably down-regulated, suggesting a possible role in heart muscle disease, though its function in the heart remains unclear.
- NR4A2 is significantly down-regulated in heart failure patients
- Altered genes affect energy production and cell death pathways
- Findings may point to new heart disease mechanisms
- Results were confirmed with independent testing methods
- NR4A2's role in the heart is unknown but potentially important
Generation and properties of a new human ventral mesencephalic neural stem cell line.
Villa A, Liste I, Courtois ET, Seiz EG, Ramos M, Meyer M, Juliusson B, Kusk P, Martínez-Serrano A
This study created a new human neural stem cell line from the midbrain region that reliably develops into dopamine-producing neurons, including those with key markers linked to Parkinson's disease. The cells maintain their identity and function, making them useful for studying human dopaminergic neurons and testing potential Parkinson's treatments.
- New human stem cell line from midbrain region
- Produces dopamine-making neurons (12% TH+)
- Retains key Parkinson's-related markers like NURR1 and PITX3
- Can be used to test Parkinson's therapies and drugs
- Stable and scalable for research use
Characterisation of a novel NR4A2 mutation in Parkinson's disease brain.
Sleiman PM, Healy DG, Muqit MM, Yang YX, Van Der Brug M, Holton JL, Revesz T, Quinn NP, Bhatia K, Diss JK, Lees AJ, Cookson MR, Latchman DS, Wood NW
A new mutation in the NR4A2 gene reduces the gene's activity in the brain, leading to lower levels of proteins essential for nerve cell function and survival. This mutation is linked to Parkinson's disease and likely causes harm by disrupting key brain development and communication pathways.
- NR4A2 mutation reduces gene activity in brain tissue
- Mutant gene produces less protein needed for nerve health
- Affected genes are critical for brain development and signaling
- Mutation impairs protection against cell death
- Findings suggest the mutation directly causes disease
Immunocytochemical expression of dopamine-related transcription factors Pitx3 and Nurr1 in prenatally stressed adult rats.
Katunar MR, Saez T, Brusco A, Antonelli MC
Prenatal stress in rats leads to increased levels of dopamine-related transcription factors Nurr1 and Pitx3 in brain regions critical for dopamine production, which may be the brain's attempt to compensate for reduced dopamine function later in life.
- Prenatal stress increases Nurr1 and Pitx3 in key dopamine brain areas
- This increase may help compensate for lower dopamine levels
- Changes were seen in the ventral tegmental area, not substantia nigra
- These transcription factors support dopamine neuron development and function
- Findings suggest potential biological pathways for intervention
Expression of the nerve growth factor-induced gene B-beta in the developing rat brain and retina.
Li Y, Ohashi R, Naito M
NGFI-Bbeta (Nurr1) is active in developing brain and retina cells in rats, appearing before birth and continuing after birth, where it helps guide neurons to mature and specialize. The protein is not found in dividing cells, indicating it plays a role in the final stages of neuron development.
- NGFI-Bbeta appears in rat brain and retina before birth
- It marks neurons that are no longer dividing
- It helps neurons mature and specialize
- Found in key brain areas like cortex and midbrain
- May guide development of vision and brain function
Haplotypes of the NR4A2/NURR1 gene and cardiovascular disease: the Rotterdam Study.
Kardys I, van Tiel CM, de Vries CJ, Pannekoek H, Uitterlinden AG, Hofman A, Witteman JC, de Maat MP
NR4A2 gene variations were not linked to heart attacks, artery thickening, or other major cardiovascular markers in older adults. However, some haplotypes were weakly tied to calcium buildup in arteries and had small effects on cholesterol and blood pressure.
- NR4A2 variants not linked to heart attacks or stroke risk
- Possible weak link to artery calcification
- Haplotypes affect HDL cholesterol and blood pressure slightly
- No strong evidence for NR4A2 role in major cardiovascular disease
- Findings may inform future research on NR4A2 pathways
Nurr1 expression and its modulation in microglia.
Fan X, Luo G, Ming M, Pu P, Li L, Yang D, Le W
Nurr1, a protein linked to dopamine neuron development, is present in microglia—immune cells in the brain—and increases when these cells are activated. This rise is controlled by specific signaling pathways, and Nurr1 moves into the cell's nucleus during activation, suggesting a role in regulating microglial responses.
- Nurr1 is found in microglia, not just neurons
- Activation increases Nurr1 levels and triggers its movement to the nucleus
- ERK, JNK, and PI3K/Akt pathways control Nurr1 expression
- Blocking these pathways reduces Nurr1 increase
- This may influence how microglia respond to brain inflammation
Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles.
Carletti MZ, Christenson LK
The study identifies rapid changes in gene expression in mouse egg cells after a hormone surge, including the immediate activation of transcription factors like NR4A2, which help control ovulation and hormone production. These early gene responses may be key to starting the process of egg release and development of the corpus luteum.
- NR4A2 is rapidly turned on by hormone signals in egg cells
- Many early genes activated are transcription factors that control other genes
- NR4A2 and related genes are likely critical for egg development and ovulation
- This process happens within one hour of hormone surge
- Findings may help understand fertility and hormone-related disorders
Inhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR.
Wang T, Jiang Q, Chan C, Gorski KS, McCadden E, Kardian D, Pardoll D, Whartenby KA
Blocking the MINOR gene in dendritic cells prevents their death after activation, which extends their lifespan and improves their ability to stimulate immune responses, potentially making cancer vaccines more effective.
- MINOR gene triggers death in activated dendritic cells
- Blocking MINOR reduces cell death and prolongs dendritic cell survival
- This could make dendritic cell vaccines more powerful
- The approach uses a lentiviral siRNA to silence MINOR expression
- Findings may improve ex vivo-generated DC vaccine potency
An 8.9 Mb 19p13 duplication associated with precocious puberty and a sporadic 3.9 Mb 2q23.3q24.1 deletion containing NR4A2 in mentally retarded members of a family with an intrachromosomal 19p-into-19q between-arm insertion.
Lybaek H, Ørstavik KH, Prescott T, Hovland R, Breilid H, Stansberg C, Steen VM, Houge G
A rare genetic deletion on chromosome 2 that includes the NR4A2 gene is linked to severe intellectual disability in a family, suggesting NR4A2 plays a key role in brain development. The same deletion was found in multiple affected relatives, supporting its importance in causing neurodevelopmental issues. This finding strengthens the connection between NR4A2 and human neurodevelopmental disorders.
- NR4A2 is a critical gene for brain development
- A 3.9 Mb deletion on 2q23.3q24.1 includes NR4A2
- This deletion is linked to severe intellectual disability
- The deletion was found in multiple affected family members
- NR4A2 loss likely contributes to neurodevelopmental symptoms
Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression.
Jacobs FM, van Erp S, van der Linden AJ, von Oerthel L, Burbach JP, Smidt MP
Pitx3 helps activate Nurr1, a key gene for dopamine neurons, by releasing a brake that keeps Nurr1 turned off. Without Pitx3, Nurr1 cannot properly turn on genes needed for dopamine neuron development. This interaction could inform future therapies for Parkinson's disease and stem cell treatments.
- Pitx3 activates Nurr1 by removing a repressive brake
- Nurr1 alone cannot drive dopamine neuron development
- Blocking HDACs can bypass the need for Pitx3
- This mechanism is critical for dopamine neuron formation
- Findings may guide stem cell therapies for Parkinson's
Expression of layer-specific markers in the adult neocortex of BCNU-Treated rat, a model of cortical dysplasia.
Moroni RF, Inverardi F, Regondi MC, Watakabe A, Yamamori T, Spreafico R, Frassoni C
This study used a rat model of cortical dysplasia to show that brain layering is disrupted, with abnormal neurons forming clusters that still show some layer-like organization. The findings help explain how mispositioned neurons develop and may guide future research into human cortical malformations.
- Cortical thinning mainly affects superficial brain layers
- Heterotopic neuron clusters show early layer patterns
- Dysmorphic neurons in surface layers are actually from deeper layers
- Layer-specific markers help track abnormal brain development
- Findings may improve understanding of human cortical dysplasia
Role of Nurr1 and Ret in inducing rat embryonic neural precursors to dopaminergic neurons.
Li L, Su Y, Zhao C, Xu Q
Nurr1 drives the development of dopamine-producing neurons in rat brain cells, and it boosts the activity of Ret, which helps mature these neurons. Together, Nurr1 and Ret work as a team to increase dopamine neuron formation and function.
- Nurr1 directly increases dopamine neuron development
- Nurr1 activates Ret expression
- Ret helps mature dopamine neurons by boosting dopamine transporter
- Both genes work together in dopamine neuron formation
- This interaction may inform future therapies for dopamine-related disorders
A simple and efficient method for generating Nurr1-positive neuronal stem cells from human wisdom teeth (tNSC) and the potential of tNSC for stroke therapy.
Yang KL, Chen MF, Liao CH, Pang CY, Lin PY
Neural stem cells can be easily grown from human wisdom teeth and survive after being transplanted into rat brains injured by stroke, leading to improved neurological function. These cells express Nurr1, a gene linked to NR4A2-related syndrome, suggesting potential for future therapies.
- Wisdom teeth contain stem cells that become Nurr1-positive neurons
- Transplanted cells survive and improve stroke recovery in rats
- Nurr1 expression links this work to NR4A2-related syndrome
- Method is simple and uses common dental tissue
- Potential for future cell-based therapies in neurodevelopmental disorders
Terminal differentiation ofmesodiencephalic dopaminergic neurons: the role of Nurr1 and Pitx3.
Smidt MP, Burbach JP
Nurr1 and Pitx3 are critical transcription factors that guide the development and maturation of midbrain dopamine neurons, which are essential for movement control and are affected in disorders like Parkinson's disease. These proteins regulate genes involved in dopamine production, neuron survival, and proper wiring of the brain's reward and motor circuits.
- Nurr1 and Pitx3 control dopamine neuron development
- They ensure proper dopamine production and neuron survival
- These factors are vital for motor and reward brain circuits
- Dysfunction may contribute to Parkinson's-like symptoms
[Differentiation of dofaminergic neurons from the human embryonal nerve cells in culture].
Tsymbaliuk VI, Vasyl'ieva IH, Oleksenko NP, Chopyk NH, Tsiubko OI, Halanta OS
Researchers successfully grew dopamine-producing neurons from human embryonic nerve cells in the lab, increasing their proportion from about 6% to 23% over time. This method could produce cell material enriched with dopamine neuron precursors for potential use in transplantation therapies.
- Dopamine neurons increased from 6% to 23% in culture
- Nurr1 and Lmx1b levels dropped, TH increased
- Culture conditions drive dopamine neuron development
- Potential for cell-based therapies for dopamine loss
- Results support future transplantation strategies
NR4A Orphan Nuclear Receptors in Cardiovascular Biology.
Zhao Y, Bruemmer D
NR4A receptors, including Nurr1 (NR4A2), play key roles in regulating genes involved in vascular biology, metabolism, and inflammation, with emerging evidence linking them to cardiovascular health and disease. These receptors are rapidly activated by environmental signals and influence processes like atherosclerosis and vascular remodeling.
- NR4A2 (Nurr1) regulates genes in blood vessel health and disease
- NR4A receptors respond quickly to environmental changes
- They influence inflammation, metabolism, and vascular remodeling
- NR4A2 activity is controlled by gene expression and protein modifications
- These receptors are linked to conditions like atherosclerosis
Whole-genome microarray analysis identifies up-regulation of Nr4a nuclear receptors in muscle and liver from diet-restricted rats.
Oita RC, Mazzatti DJ, Lim FL, Powell JR, Merry BJ
Dietary restriction in rats increases levels of NR4A2 and related genes in muscle and liver, which are involved in metabolism and insulin sensitivity, suggesting a potential role in healthy aging and metabolic adaptation.
- Dietary restriction boosts NR4A2 in muscle and liver
- NR4A2 helps regulate metabolism and insulin response
- These changes may support healthier aging
- NR4A2 targets include genes linked to energy use
- Findings may inform therapies for metabolic health
Lmx1b-controlled isthmic organizer is essential for development of midbrain dopaminergic neurons.
Guo C, Qiu HY, Shi M, Huang Y, Johnson RL, Rubinstein M, Chen SD, Ding YQ
Lmx1b is not needed inside midbrain dopamine neurons for their development or survival; instead, it is essential for the midbrain-hindbrain boundary to send signals that create these neurons. When this signaling center is restored, dopamine neurons form normally even without Lmx1b in the neurons themselves.
- Lmx1b is not required in dopamine neurons to form or survive
- The midbrain-hindbrain signaling center needs Lmx1b to function
- Restoring the signaling center brings back dopamine neurons
- Lmx1b loss affects dopamine neurons indirectly, not directly
Absence of age-related changes in nigral dopaminergic neurons of Asian Indians: relevance to lower incidence of Parkinson's disease.
Alladi PA, Mahadevan A, Yasha TC, Raju TR, Shankar SK, Muthane U
Asian Indians do not lose dopamine-producing neurons in the brain's substantia nigra as they age, unlike people of other ethnicities. This stability may explain why Asian Indians have a lower rate of Parkinson's disease.
- No age-related loss of dopamine neurons in Asian Indians
- Dopamine-related proteins remain stable with age
- No signs of neuron death or shrinkage
- May explain lower Parkinson's disease rates
- Suggests protective biological factors
Glutamatergic nonpyramidal neurons from neocortical layer VI and their comparison with pyramidal and spiny stellate neurons.
Andjelic S, Gallopin T, Cauli B, Hill EL, Roux L, Badr S, Hu E, Tamás G, Lambolez B
Neocortical layer VI contains a diverse group of glutamatergic neurons that are not pyramidal and project within the cortex. These neurons show varied shapes and electrical behaviors, with some expressing Nurr1, a gene linked to NR4A2-related disorders. Their electrical patterns suggest functional similarities across different cortical layers, independent of structure or connections.
- Layer VI has glutamatergic nonpyramidal neurons
- Some express Nurr1, a marker tied to NR4A2
- Electrical patterns vary beyond neuron shape or location
- These neurons may influence cortical circuits in NR4A2-related conditions
- Findings could inform brain circuit therapies
[Association of the polymorphisms in NURR1 gene with Parkinson's disease].
Wu Y, Peng R, Chen W, Zhang J, Li T, Wang Y, Gou Y, Yuan G
A genetic variation in the NURR1 gene, specifically the IVS6+18insG polymorphism, is linked to early-onset Parkinson's disease in a Han Chinese population, suggesting it may increase risk for developing the condition before age 50. The other tested genetic site showed no association with Parkinson's disease in this group.
- IVS6+18insG variant linked to early-onset Parkinson's
- Higher frequency of 3G/2G genotype in young-onset PD patients
- No link found between c.-2922(C)2-3 and Parkinson's in this group
- Findings suggest a genetic risk factor for early Parkinson's
Visualization of spatiotemporal differentiation of dopaminergic interneurons in adult mouse olfactory bulb using transgenic mice.
Saino-Saito S
This study uses genetically modified mice to track how dopamine-producing neurons form in the adult mouse brain's smell center. It finds that a gene called Nurr1, not other genes, controls dopamine production in these neurons, and that environmental factors like smell influence their development.
- Nurr1 regulates dopamine production in adult mouse smell neurons
- Dopamine neuron development starts before cells reach their final position
- Smell experience affects dopamine neuron maturation
- Genetic tools help track neuron development in real time
- Findings may inform treatments for dopamine-related brain disorders
Novel markers reveal subpopulations of subplate neurons in the murine cerebral cortex.
Hoerder-Suabedissen A, Wang WZ, Lee S, Davies KE, Goffinet AM, Rakić S, Parnavelas J, Reim K, Nicolić M, Paulsen O, Molnár Z
This study identifies new molecular markers for subplate neurons in mouse brains, which may help distinguish different subpopulations of these cells. These findings could improve understanding of how early brain development goes awry in neurodevelopmental disorders.
- New markers identify distinct subpopulations of subplate neurons
- NR4A2 (NURR1) is specifically expressed in subplate cells
- Subplate cell organization is disrupted in mouse models of brain development disorders
- These markers may aid in diagnosing brain developmental abnormalities
- Findings could inform future therapies targeting early cortical development