Moxonidine ameliorates cardiac injury in rats with metabolic syndrome by regulating autophagy.
El-Sayed SS, Rezq S, Alsemeh AE, Mahmoud MF
Moxonidine reduces heart damage in rats with metabolic syndrome by boosting a protective cellular cleanup process called autophagy, which is linked to the NR4A2 protein. This effect depends on activation of the I1R receptor and involves restoring levels of NR4A2 and key autophagy markers.
- Moxonidine protects the heart in metabolic syndrome
- It works by boosting autophagy via NR4A2
- Effect requires I1R receptor activation
- Restores autophagy markers like LC3 and p62
- Blocking I1R reverses the benefits
Functional Interaction Between α-Synuclein and Nurr1 in Dopaminergic Neurons.
Argyrofthalmidou M, Polissidis A, Karaliota S, Papapanagiotou I, Sotiriou E, Manousaki M, Papadopoulou-Daifoti Z, Spillantini MG, Stefanis L, Vassilatis DK
Mice with both reduced Nurr1 levels and overexpression of a truncated form of alpha-synuclein in dopamine-producing neurons show lasting dopamine system dysfunction, including reduced dopamine in the striatum and abnormal behavior, even without full Parkinson’s disease symptoms. This suggests that imbalances between these two proteins disrupt brain function in ways that may contribute to neuropsychiatric features of Parkinson’s disease.
- Nurr1 and alpha-synuclein levels are critical for dopamine neuron health
- Reduced Nurr1 plus alpha-synuclein overexpression causes lasting dopamine dysfunction
- Mice showed abnormal behavior and energy use, even without classic Parkinson’s signs
- Dopamine transporter changes suggest disrupted dopamine regulation
- Findings may explain psychiatric symptoms in Parkinson’s and related disorders
The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.
Alsanie WF, Abdelrahman S, Alhomrani M, Gaber A, Alosimi EA, Habeeballah H, Alkhatabi HA, Felimban RI, Hauser CAE, Tayeb HH, Alamri AS, Alamri A, Raafat BM, Alswat KA, Althobaiti YS, Asiri YA
Prenatal exposure to quetiapine fumarate disrupts the development of dopaminergic neurons in mouse embryos by reducing key genes involved in their formation and function, while increasing others like Nurr1. This suggests potential risks to fetal brain development, especially for genes linked to movement, behavior, and cognition.
- Quetiapine harms dopaminergic neuron development in embryos
- Critical genes for dopamine neurons are suppressed
- Nurr1, a protective gene, increases in response
- Low-dose quetiapine still affects neuron structure
- Findings may guide safer antipsychotic use in pregnancy
BDNF-modified human umbilical cord mesenchymal stem cells-derived dopaminergic-like neurons improve rotation behavior of Parkinson's disease rats through neuroprotection and anti-neuroinflammation.
Jiang Z, Wang J, Sun G, Feng M
Transplanting brain-derived neurotrophic factor (BDNF)-modified stem cells that become dopamine-producing neurons improves movement in Parkinson's disease rats by protecting brain cells and reducing inflammation. The treatment works through two key pathways: one that supports neuron survival and another that calms harmful brain inflammation.
- BDNF-modified stem cells improve movement in Parkinson's rats
- Cells protect brain neurons and reduce inflammation
- Works through BDNF and Hsp60 signaling pathways
- Increases dopamine and key brain repair proteins
- Offers a potential therapy approach for Parkinson's
Newly regenerated dopaminergic neurons in 6-OHDA-lesioned adult zebrafish brain proliferate in the Olfactory bulb and telencephalon, but migrate to, differentiate and mature in the diencephalon.
Vijayanathan Y, Hamzah NM, Lim SM, Lim FT, Tan MP, Majeed ABA, Ramasamy K
Zebrafish can regenerate dopamine-producing neurons after brain injury by first creating new cells in the olfactory bulb and front brain, which then move to the deeper brain region where they mature into functional dopamine neurons. This process involves temporary changes in key genes like nr4a2a (nurr1) and foxa2, which are essential for dopamine neuron development.
- New dopamine neurons form in zebrafish after brain injury
- Cells start in olfactory bulb and front brain, then move to deep brain
- Regeneration requires temporary changes in nr4a2a and foxa2 genes
- New neurons mature and become functional over 30 days
- Astrocytes help support the repair process
Construction of an immune-related signature for predicting the ischemic events in patients undergoing carotid endarterectomy.
Li S, Zhang Q, Weng L, Li J
This study found that a set of immune-related genes, including NR4A2, can predict the risk of stroke after carotid surgery. The model uses seven genes to identify patients at higher risk for ischemic events, with stronger immune activity linked to better outcomes.
- NR4A2 is part of a 7-gene signature predicting stroke risk after carotid surgery
- Higher immune activity correlates with lower risk of ischemic events
- The gene model may help guide clinical decisions post-surgery
- The signature was validated in patient data and linked to immune response
- A nomogram based on the genes could support future clinical use
Transcriptomic networks of gba3 governing specification of the dopaminergic neurons in zebrafish embryos.
Kumar A, Rhee M
The gene gba3 plays a key role in guiding the development of dopamine-producing neurons in zebrafish embryos, with its activity essential for proper formation of brain regions involved in movement and reward. Disrupting gba3 reduces levels of critical dopamine-related genes, but restoring gba3 can reverse these effects.
- gba3 is vital for dopamine neuron development in zebrafish
- Loss of gba3 reduces key dopamine genes like nurr1 and th
- gba3 function is specific to midbrain and hindbrain regions
- Restoring gba3 can rescue developmental defects
- Findings may inform future therapies for NR4A2-related disorders
Parkinson's disease-associated, sex-specific changes in DNA methylation at PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), and NR4A2 (NURR1) in cortical neurons.
Kochmanski J, Kuhn NC, Bernstein AI
This study found that DNA methylation changes in genes linked to Parkinson's disease, including NR4A2 (NURR1), differ between men and women in brain neurons. These changes may influence how the disease develops and progresses, especially in pathways related to brain cell function and communication. The findings highlight the importance of considering both sex and cell type in understanding Parkinson's disease biology.
- NR4A2 methylation changes are sex-specific in Parkinson's brain neurons
- DNA methylation differences affect genes involved in neuron function
- Sex and cell type matter in Parkinson's epigenetic research
- These changes may influence disease progression and severity
Ukgansan Protects Dopaminergic Neurons against MPTP-Induced Neurotoxicity via the Nurr1 Signaling Pathway.
Chae IC, Jang JH, Seol IC, Kim YS, Park G, Yoo HR
Ukgansan protects dopamine-producing brain cells from damage in a Parkinson's disease model by boosting the activity of the Nurr1 protein, which helps maintain dopamine levels and improves movement symptoms. This suggests Ukgansan may slow disease progression and reduce motor problems.
- Ukgansan activates Nurr1, a key protein for dopamine neuron survival
- It reduces neuron death and dopamine loss in Parkinson's models
- Improves motor function in mice exposed to neurotoxins
- May offer a natural alternative to current Parkinson's treatments
- Supports further study of Ukgansan for neurodegenerative conditions
Transfer of neuron-derived α-synuclein to astrocytes induces neuroinflammation and blood-brain barrier damage after methamphetamine exposure: Involving the regulation of nuclear receptor-associated protein 1.
Huang J, Ding J, Wang X, Gu C, He Y, Li Y, Fan H, Xie Q, Qi X, Wang Z, Qiu P
Methamphetamine exposure causes neurons to release excess alpha-synuclein, which is taken up by astrocytes, leading to reduced Nurr1 levels, brain inflammation, and damage to the blood-brain barrier. Boosting Nurr1 or blocking alpha-synuclein can protect the barrier and reduce brain injury.
- Methamphetamine increases alpha-synuclein in neurons
- Alpha-synuclein spreads to astrocytes and lowers Nurr1
- Low Nurr1 causes brain inflammation and blood-brain barrier damage
- Restoring Nurr1 or blocking alpha-synuclein protects the barrier
- Nurr1 and alpha-synuclein are potential treatment targets
Neuropilin-1 (NRP1) expression distinguishes self-reactive helper T cells in systemic autoimmune disease.
Raveney BJ, El-Darawish Y, Sato W, Arinuma Y, Yamaoka K, Hori S, Yamamura T, Oki S
Neuropilin-1 (NRP1) is a surface marker that identifies self-reactive helper T cells involved in systemic autoimmune diseases like lupus. These cells are linked to disease severity and can trigger or worsen autoimmunity, while reducing NRP1-expressing cells improves symptoms in mouse models and human patients.
- NRP1 marks self-reactive T cells in autoimmune disease
- NRP1+ T cells drive disease in mice and humans
- Targeting NRP1 reduces autoimmune symptoms
- NR4A2 deficiency reduces NRP1+ cells and autoimmunity
- NRP1 could guide new autoimmune treatments
Transplantation of human cord blood-derived multipotent stem cells (CB-SCs) enhances the recovery of Parkinson in rats.
Tang X, Li H, An B, Ma H, Huang N, Li X
Transplanting human cord blood stem cells helps Parkinson's rats recover by replacing lost dopamine neurons and improving movement, with most transplanted cells becoming dopamine-producing and surviving in the brain.
- Cord blood stem cells become dopamine neurons in rats
- Transplanted cells survive and produce dopamine in the brain
- Rats show better movement recovery after treatment
- Higher dopamine levels found in treated brains
- Cells were found in key brain areas for movement control
Transcriptomic analysis in the striatum reveals the involvement of Nurr1 in the social behavior of prenatally valproic acid-exposed male mice.
Kim H, Woo RS, Yang EJ, Kim HB, Jo EH, Lee S, Im H, Kim S, Kim HS
Increased Nurr1 levels in the striatum are linked to social behavior and synaptic problems in a mouse model of autism caused by prenatal valproic acid exposure. Reducing Nurr1 or blocking it with a drug improved social behavior and brain cell connections, suggesting Nurr1 may be a key target for treating autism-related symptoms.
- Nurr1 is overactive in the striatum of autism-like mice
- Lowering Nurr1 improved social behavior and brain cell connections
- A drug that blocks Nurr1 caused autism-like symptoms in normal mice
- Nurr1 levels are also high in another autism mouse model
- Nurr1 may be a promising treatment target for autism
Two novel heterozygous truncating variants in NR4A2 identified in patients with neurodevelopmental disorder and brief literature review.
Song X, Xu W, Xiao M, Lu Y, Lan X, Tang X, Xu N, Yu G, Zhang H, Wu S
NR4A2 gene changes cause neurodevelopmental disorders with features like developmental delay, language problems, and ADHD. Two new variants in this gene were found in patients, both affecting protein production and likely causing disease, with different impacts on protein levels and function.
- NR4A2 variants cause neurodevelopmental disorders
- Two new variants disrupt protein production
- One variant causes loss of protein, the other increases it unexpectedly
- Symptoms vary based on where the mutation occurs in the gene
- Findings support NR4A2 as a key gene in these conditions
Bioinformatics analysis of mRNA profiles and identification of microRNA-mRNA network in CD4+ T cells in seasonal allergic rhinitis.
Jin P, Zhang H, Zhu X, Sun K, Jiang T, Shi L, Zhi L, Zhang H
NR4A2 is one of only three genes consistently changed in CD4+ T cells during and outside the pollen season in seasonal allergic rhinitis, suggesting it plays a key role in immune dysfunction. The study identifies NR4A2 as part of a larger network involving microRNAs and other genes linked to immune activation.
- NR4A2 is dysregulated in allergic rhinitis CD4+ T cells
- NR4A2 is part of a network tied to immune cell activation
- MicroRNA hsa-miR-29b-3p may regulate NR4A2
- Findings point to potential immune targets for treatment
- Results are from human immune cells in a real disease context
Adeno-associated virus (AAV) 9-mediated gene delivery of Nurr1 and Foxa2 ameliorates symptoms and pathologies of Alzheimer disease model mice by suppressing neuro-inflammation and glial pathology.
Yang Y, Seok MJ, Kim YE, Choi Y, Song JJ, Sulistio YA, Kim SH, Chang MY, Oh SJ, Nam MH, Kim YK, Kim TG, Im HI, Koh SH, Lee SH
Delivering the Nurr1 and Foxa2 genes using AAV9 virus improved memory and reduced brain damage in Alzheimer's disease mouse models by calming harmful brain inflammation and fixing dysfunctional glial cells.
- Nurr1 and Foxa2 genes reduce brain inflammation and glial damage
- AAV9 delivers genes directly to the brain
- Treatment improved memory and cognitive function in mice
- Benefits come from fixing glial cell problems
- This approach targets underlying disease processes
Prenatal Exposure to Gabapentin Alters the Development of Ventral Midbrain Dopaminergic Neurons.
Alsanie WF, Abdelrahman S, Alhomrani M, Gaber A, Habeeballah H, Alkhatabi HA, Felimban RI, Hauser CAE, Tayeb HH, Alamri AS, Raafat BM, Anwar S, Alswat KA, Althobaiti YS, Asiri YA
Prenatal exposure to gabapentin disrupts the development of dopamine-producing brain cells in fetuses, affecting their shape, gene activity, and energy production. This suggests gabapentin may increase the risk of neurodevelopmental issues in children born to mothers who take it during pregnancy.
- Gabapentin harms fetal dopamine neuron development
- Alters genes linked to brain development and function
- Reduces energy production in developing brain cells
- May increase neurodevelopmental risks in children
- Use during pregnancy should be carefully considered
Identification of Immune Microenvironment Changes and the Expression of Immune-Related Genes in Liver Cirrhosis.
Liu Y, Dong Y, Wu X, Wang X, Niu J
This study found that liver cirrhosis is linked to major changes in immune cells, including fewer CD8+ T cells and NK cells, and more memory CD4+ T cells. It identified NR4A2 as one of four key transcription factors involved in regulating immune responses in liver fibrosis.
- CD8+ T cells and NK cells are reduced in cirrhosis
- Memory CD4+ T cells increase in liver tissue
- NR4A2 is linked to immune regulation in liver fibrosis
- Four transcription factors, including NR4A2, may control immune cell function
- Immune-related genes and pathways are altered in cirrhosis
A Novel Mechanism of Coactivator Recruitment by the Nurr1 Nuclear Receptor.
Daffern N, Radhakrishnan I
Nurr1, a protein linked to neurodevelopmental disorders, uses a specific part of its structure to directly recruit coactivator proteins that help turn on genes. This interaction occurs through a helical segment binding to a pocket on the coactivator, a mechanism that may also apply to other transcription factors.
- Nurr1 uses a helix in its AF1 domain to bind coactivators
- The binding site overlaps with where STAT6 attaches, suggesting shared mechanisms
- This direct recruitment could influence gene activity in NR4A2-related conditions
- Understanding this may help design therapies targeting Nurr1 function
NURR1 expression regulates retinal pigment epithelial-mesenchymal transition and age-related macular degeneration phenotypes.
Yao PL, Parmar VM, Choudhary M, Malek G
NURR1 is a key regulator of retinal health, and its decline with age contributes to retinal pigment epithelial cells turning into harmful, scar-like cells, a process linked to age-related macular degeneration (AMD). Boosting NURR1 activity with a drug called IP7e reduced cell damage, inflammation, and vision loss in mouse models of AMD.
- NURR1 levels drop with age in eye cells, driving AMD-related damage
- Low NURR1 leads to harmful changes in retinal cells
- Activating NURR1 with IP7e improved eye function in AMD models
- NURR1 helps control inflammation and fat buildup in the retina
- Targeting NURR1 may lead to new AMD treatments
Medicinal Chemistry and Chemical Biology of Nurr1 Modulators: An Emerging Strategy in Neurodegeneration.
Willems S, Merk D
Nurr1 is a key protein that protects brain cells and reduces brain inflammation, making it a promising target for treating neurodegenerative diseases like Parkinson’s. Recent advances have identified small molecules that can activate Nurr1, offering potential new therapies.
- Nurr1 protects brain cells and reduces inflammation
- Small molecules can activate Nurr1, potentially treating Parkinson’s
- New drug candidates are being developed to target Nurr1
- This approach may slow or stop neurodegeneration
Recruitment of the CoREST transcription repressor complexes by Nerve Growth factor IB-like receptor (Nurr1/NR4A2) mediates silencing of HIV in microglial cells.
Ye F, Alvarez-Carbonell D, Nguyen K, Leskov K, Garcia-Mesa Y, Sreeram S, Valadkhan S, Karn J
Nurr1 (NR4A2) helps shut down HIV in brain immune cells by binding to the virus's DNA and bringing in repressor complexes that silence viral activity. This process reduces inflammation and supports brain cell stability, suggesting Nurr1 activators could help treat HIV-related brain problems.
- Nurr1 directly silences HIV in brain immune cells
- Nurr1 recruits repressor complexes to block HIV gene activity
- Activating Nurr1 reduces inflammation and supports brain health
- Nurr1 helps maintain HIV in a dormant state
- Nurr1 activators may treat HIV brain complications
Transcriptome landscapes that signify Botrylloides leachi (Ascidiacea) torpor states.
Hyams Y, Panov J, Rosner A, Brodsky L, Rinkevich Y, Rinkevich B
The study identifies a unique gene expression profile in the sea squirt Botrylloides leachi during torpor, a state of suspended animation. NR4A2 and several other genes linked to stress response, development, and immunity are upregulated, suggesting a coordinated molecular program for survival in harsh conditions.
- NR4A2 is upregulated during torpor in sea squirts
- Torpor involves dramatic gene expression changes and cell type shifts
- WNT signaling triggers early arousal from torpor
- Upregulated genes include developmental and stress-response factors
- Findings may inform mechanisms of cellular dormancy and recovery
Prolonged cardiac NR4A2 activation causes dilated cardiomyopathy in mice.
Ashraf S, Taegtmeyer H, Harmancey R
In mice, overactivating the NR4A2 gene in heart cells causes heart failure within 40 days by forcing heart cells to restart their cell cycle without dividing, leading to abnormal cell growth, loss of heart function, and cell death. This suggests NR4A2 plays a key role in heart cell regeneration and may be a target for treating heart disease.
- NR4A2 overactivation causes heart failure in mice
- Heart cells restart division but don’t split, becoming multi-nucleated
- NR4A2 pushes heart cells back to a fetal state
- Cells die due to failed division and stress
- NR4A2 may control heart cell regeneration
A Nurr1 ligand C-DIM12 attenuates brain inflammation and improves functional recovery after intracerebral hemorrhage in mice.
Kinoshita K, Yoshimizu A, Ichihara Y, Ushida K, Kotani S, Kurauchi Y, Seki T, Katsuki H
C-DIM12, a compound that activates the Nurr1 protein, reduces brain inflammation and helps mice recover neurological function after a stroke-like brain bleed. It protects brain cells, preserves nerve connections, and works by blocking a harmful enzyme linked to inflammation.
- C-DIM12 improves brain recovery after hemorrhage in mice
- It reduces brain inflammation and protects neurons
- It preserves nerve fiber structure and function
- It blocks a key inflammatory enzyme (iNOS)
- Results support Nurr1 activation as a potential therapy
Embelin and levodopa combination therapy for improved Parkinson's disease treatment.
Ramachandra VH, Sivanesan S, Koppal A, Anandakumar S, Howell MD, Sukumar E, Vijayaraghavan R
Embelin, when combined with levodopa, reduces oxidative stress and gut damage in a mouse model of Parkinson's disease, restores levels of key proteins like Nurr1 and tyrosine hydroxylase, and may help slow disease progression by targeting alpha-synuclein.
- Embelin reduces oxidative stress and gut damage
- Combining embelin with levodopa boosts protective protein levels
- Embelin binds to alpha-synuclein, a key protein in Parkinson’s
- The treatment preserved dopaminergic neurons in the brain
- Findings suggest a potential new therapy for Parkinson’s disease
Effects of bis (2-butoxyethyl) phthalate on adrenocortical function in male rats in puberty partially via down-regulating NR5A1/NR4A1/NR4A2 pathways.
Liu M, Chen H, Dai H, Wang Y, Li J, Tian F, Li Z, Ge RS
Exposure to BBOP in male rats during puberty disrupts adrenal hormone production by reducing key steroid-making genes and proteins, including NR4A2, and impairing cellular energy and antioxidant systems, likely through reduced signaling via AKT and ERK pathways and increased oxidative stress.
- BBOP reduces adrenal hormone production in pubertal male rats
- NR4A2 and other steroid genes are down-regulated by BBOP
- BBOP increases oxidative stress and cell death in adrenal cells
- Signaling pathways AKT and ERK are suppressed by BBOP
- BBOP disrupts adrenal function without changing gland size
The role of NURR1 in metabolic abnormalities of Parkinson's disease.
Al-Nusaif M, Yang Y, Li S, Cheng C, Le W
NURR1 plays a key role in maintaining brain cell metabolism and is linked to Parkinson's disease development. Low NURR1 levels disrupt energy production in brain cells, contributing to disease progression.
- NURR1 regulates energy use in brain cells
- Low NURR1 harms dopamine-producing neurons
- Metabolic issues may start before Parkinson's symptoms appear
- Targeting NURR1 could lead to new treatments
Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation.
Pulcrano S, De Gregorio R, De Sanctis C, Lahti L, Perrone-Capano C, Ponti D, di Porzio U, Perlmann T, Caiazzo M, Volpicelli F, Bellenchi GC
miR-204/211 acts as a molecular switch that controls when the Nurr1 gene turns on during the development of dopamine-producing brain cells. This process is regulated by the Lmx1a protein, which helps time the activation of Nurr1, a key gene for mature dopamine neurons.
- miR-204/211 delays Nurr1 activation in developing dopamine neurons
- Lmx1a boosts miR-204/211 levels to time Nurr1 expression
- This timing is critical for proper dopamine neuron development
- Disruptions in this pathway may affect brain function in NR4A2-related disorders