Momordicine I, a triterpene from bitter melon (Momordica charantia L.), ameliorates alcohol-associated liver disease: research on the possible liver benefits.
Hou Y, Wang SY, Xu ZY, Xin G, Zhao GY, Sun HM
Momordicine I, a compound from bitter melon, protects the liver in alcohol-related disease by boosting Nurr1, a protein linked to NR4A2. It reduces fat buildup, improves energy production in liver cells, and blocks harmful inflammation. Without Nurr1, the benefits of Momordicine I disappear.
- Momordicine I boosts Nurr1, which is linked to NR4A2
- It reduces liver fat and improves mitochondrial function
- It blocks inflammation and cell death in liver cells
- Nurr1 is essential for Momordicine I's protective effects
- These findings suggest a potential treatment for alcohol-related liver disease
The genetic architecture of Parkinson's disease in Mexico: a systematic review.
Arias-Carrión O, Romero-Gutiérrez E, Castellanos-Juárez FX, Sandoval-Carrillo AA, Salas-Pacheco JM
This review identifies NR4A2 as one of eight genes consistently linked to Parkinson's disease in Mexican populations, with specific NR4A2 haplotypes showing protective or risk-increasing effects. The findings highlight NR4A2's role in dopaminergic signaling and mitochondrial health, suggesting potential therapeutic relevance.
- NR4A2 haplotypes are linked to Parkinson's risk in Mexicans
- Protective NR4A2 variants may improve dopamine function
- NR4A2 fits into key Parkinson's pathways like mitochondrial health
- Genetic risk varies by ancestry and needs more study
- Findings support targeting NR4A2 for future therapies
Generating graftable dopaminergic neurons by NR4A2 activation and exploring associated lncRNA signatures.
Malekmohammad L, Esfahani NMJ, Momeni Z, Esmaeili F, Khademizadeh M, Farhadieh ME, Karimi F, Keimasi M, Soleimani-Delfan A
Activating the NR4A2 gene helps create dopaminergic neurons from stem cells that can survive and function when transplanted into a Parkinson’s disease model, with increased levels of key lncRNAs linked to neuron health. These findings suggest a potential path for cell-based therapies in NR4A2-related disorders.
- NR4A2 activation produces transplantable dopaminergic neurons
- Neat1, Hotair, and Uchl1os lncRNAs increase after transplantation
- Transplanted neurons boost dopamine levels in PD models
- LncRNA patterns may support neuron survival and function
- Results support NR4A2 as a target for future therapies
Mechanistic insights into the role of nuclear receptor related-1 protein in Parkinson's disease.
Sharma V, Singh TG
Nurr1 is a critical protein for the health and survival of dopamine-producing brain cells, and its dysfunction contributes to Parkinson's disease by increasing inflammation, weakening antioxidant defenses, and impairing mitochondrial function. Restoring Nurr1 activity may protect neurons and slow disease progression, making it a promising target for new treatments.
- Nurr1 protects dopamine neurons from damage
- Low Nurr1 levels increase brain inflammation
- Nurr1 helps maintain energy and antioxidant systems
- Boosting Nurr1 could treat Parkinson's disease
- Nurr1 is a key target for future therapies
De novo identification of potent ingredients for proteasome activation in MT101-5 using an AI-driven approach.
Kim S, Han M, Kim SW, Choi JG, Park SC, Choi SI, Son M, Lee D
Diterpenes from MT101-5 boost the proteasome by activating Nurr1, helping clear toxic alpha-synuclein and protecting dopamine neurons in a mouse model of Parkinson’s disease.
- Nurr1 activation enhances proteasome function
- Diterpenes reduce alpha-synuclein clumps
- Improved motor function and neuron survival in mice
- MT101-5 ingredients show promise for Parkinson’s treatment
Forward Programming Identifies Inducers of Blood-Brain Barrier Properties in Human Pluripotent Stem Cell-Derived Endothelial Cells.
Tamhankar S, Ding Y, Hashjin FY, Boutom SM, Daneman R, Palecek SP, Shusta EV
Researchers identified specific genes that can turn stem cell-derived blood vessel cells into brain barrier cells with strong protective properties. These engineered cells show improved barrier function and are useful for studying brain diseases and testing drugs.
- NR4A2 helps create brain barrier-like cells from stem cells
- Combining NR4A2 with other genes boosts barrier strength
- These cells can model brain diseases and test treatments
- The method may help develop therapies for brain disorders
Structure-activity landscape of Nurr1 (NR4A2) modulators: medicinal chemistry strategies for neurodegenerative disease intervention.
Jaidka S, Kumar A, Singh TG, Bhatia R, Singh RK
Nurr1 is a key protein for dopamine neuron health, and drugs that activate it may help treat Parkinson's and other neurodegenerative diseases. While several compounds show promise in lab studies, none yet reliably target Nurr1 without affecting similar proteins, cross the blood-brain barrier, or consistently work in living organisms.
- Nurr1 supports dopamine neuron survival and function
- Activating Nurr1 may protect against Parkinson’s and Alzheimer’s
- Many experimental drugs also activate related proteins, causing confusion
- Current compounds lack brain penetration and consistent in vivo results
- Designing selective, brain-penetrant Nurr1 drugs remains a major challenge
The Interplay Between Nurr1 and Mitochondrial Biogenesis: Implications for Neurodegenerative Therapy.
Kaur S, Mannan A, Singh TG
Nurr1 (NR4A2) helps protect dopamine-producing brain cells by boosting mitochondrial health and reducing oxidative stress, which are key issues in Parkinson's and Alzheimer's diseases. This makes Nurr1 a promising target for therapies aimed at slowing or stopping neurodegeneration.
- Nurr1 supports brain cell survival by improving mitochondria
- It reduces oxidative damage linked to Parkinson's and Alzheimer's
- Nurr1's activity can be boosted through post-translational changes
- Targeting Nurr1 may help treat neurodegenerative diseases
- Mitochondrial dysfunction is a major factor in brain cell loss
Epigenome-wide analysis identifies DNA methylation signatures associated with the infant pupillary light reflex, a candidate intermediate phenotype for autism.
Fish LA, Gliga T, Gui A, Ali JB, Mason L, Johnson MH, Charman T, Falck-Ytter T, Jones EJH, Kandaswamy R, Happé F, Wong CCY
DNA methylation patterns in early infancy are linked to variations in the pupillary light reflex, a simple neural response that may signal early differences in brain development related to autism. The study found that methylation changes in genes like NR4A2 are associated with how quickly and how much the pupil constricts in response to light.
- DNA methylation affects pupillary light reflex timing and strength
- NR4A2 and other autism-linked genes are involved
- Changes appear as early as 9 months
- Pupillary reflex may be an early sign of neurodevelopmental differences
- Findings focus on male infants with family history of autism
Renalase stimulates aldosterone production via PMCA4b/cAMP in NCI-H295R cells.
Fu R, Huang M, Liu T, Chen Y, Li X, Jiang W
Renalase increases aldosterone production in adrenal cells by activating a signaling pathway involving PMCA4b and cAMP, which turns on the NR4A2 gene. This process does not affect cell growth but may contribute to conditions where too much aldosterone is made.
- Renalase boosts aldosterone production in adrenal cells
- It works through PMCA4b and cAMP signaling
- NR4A2 gene activity increases as a result
- No effect on cell growth, but may drive disease
- Could be a target for treating aldosterone-related disorders
Single-Cell Transcriptomics and Integrated Bioinformatic Analysis Reveal Critical Biomarkers and Immune Infiltration Characteristics in Osteoarthritis.
Gao T, Yang C, Bi Y, Zou P, Wan M, Lan S, Song Y, Xu Y
This study identifies NR4A2 and other genes as key players in osteoarthritis, linking them to inflammation and immune activity in joint cartilage. The research suggests bexarotene may target NR4A2 and related proteins, pointing to a potential treatment for osteoarthritis.
- NR4A2 is a strong biomarker and drug target in osteoarthritis
- NR4A2 correlates with immune activity in joint tissue
- Bexarotene shows promise in binding NR4A2 and related proteins
- The findings reveal new pathways driving joint degeneration
- These insights could lead to targeted therapies for osteoarthritis
Exploring the Mechanism of Shexiang Baoxin Pill in the Treatment of Ischemic Stroke: A Study Integrating Network Pharmacology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation.
Fu J, Wang Y, Li X, Dong X
Shexiang Baoxin Pill may help treat ischemic stroke by reducing inflammation and immune system overactivity through multiple active ingredients that bind to key proteins like TNF and JUN, which are involved in brain injury after stroke.
- SBP targets inflammation and immune pathways linked to stroke
- Bufalin and bufotalin bind stably to TNF and JUN proteins
- NR4A2 is one of six key targets identified in stroke
- The effect involves multiple compounds and targets working together
- Findings suggest a potential protective role in brain blood vessel damage
Targeting Nurr1 With Amodiaquine Preserves Dendritic Spines and Cognitive Function After Chronic Cerebral Hypoperfusion.
Zeng X, Xie X, Zhang J, Jia J, Huang L
Amodiaquine, a drug that activates the Nurr1 protein, improved memory and protected brain connections in rats with reduced brain blood flow, a condition linked to cognitive decline. The treatment preserved the structure of neurons and their tiny connections (dendritic spines) in the memory-related hippocampus.
- Amodiaquine boosts Nurr1 activity in the brain
- It protects neuron connections after poor blood flow
- Memory and learning improved in treated rats
- Benefits lasted up to 6 weeks after treatment
- Nurr1 activation may help prevent cognitive decline
Nurr1 Orchestrates Claustrum Development and Functionality.
Yan K, Newman AG, Lange P, Müller S, Foddis M, Koch SP, Böhm-Sturm P, Mantwill M, Finke C, Deng P, Long M, Schmitz D, Tarabykin V
Nurr1 is essential for the proper development and function of the claustrum, a brain region involved in coordinating cognition and consciousness. Without Nurr1, claustral cells misplace themselves and adopt incorrect genetic programs, disrupting brain connectivity and behavior.
- Nurr1 controls claustrum development and cell identity
- Nurr1 loss causes cells to migrate incorrectly into the insular cortex
- Claustrum connectivity and behavior are disrupted without Nurr1
- Nurr1 works by suppressing Gαs-PKA signaling
- Single-cell data confirms abnormal gene programs in mutant cells
Prolonged Loss of Oxidative Phosphorylation and Mitochondrial Mass Characterize CD66b+ Leukocytes from Patients with Sepsis.
Rodhouse C, Barrios EL, Zeumer-Spataro L, Balzano-Nogueira L, Wu R, Yu X, Tian G, Brant JO, Gauthier ML, Chen J, Hernandez-Rios M, Polcz VE, Wiggins W, Charles AM, Dirain ML, Ungaro R, Rincon J, Loftus T, Xiao F, Cai G, Moldawer LL, Maile R, Kladde MP, Efron PA, Mathews CE
People who have had sepsis continue to have immune cells with damaged mitochondria and reduced energy production for at least six months after their illness, even when they appear recovered. This long-term metabolic defect is linked to worse health outcomes and may be caused by the silencing of key genes, including NR4A2, that control mitochondrial health.
- Mitochondria in immune cells remain damaged for 6 months after sepsis
- NR4A2 and other genes controlling mitochondria are turned down
- This gene silencing may explain ongoing immune problems
- Reduced mitochondrial function predicts worse recovery
- Targeting metabolism could help restore immune health
The multiple mechanisms of NR4A2 in neurological disorders and advances in targeted therapy research.
Duan K, Yang C, Gao D, Li M, Chen M, Li H, Zeng W, Zhao L, Zhu M
NR4A2 is a key gene involved in brain development and function, and its dysfunction is linked to multiple neurological conditions including Parkinson's, Alzheimer's, autism, and stroke. Research shows that boosting NR4A2 activity may help treat these disorders through drugs, gene therapy, or cell replacement strategies.
- NR4A2 is critical for brain development and function
- Mutations in NR4A2 are linked to autism and other neurological disorders
- NR4A2-targeted therapies are being developed for treatment
- Agonists and gene therapy show promise in preclinical studies
- NR4A2 plays roles in both brain development and neurodegeneration
Essential function of Nr4a2 in subicular development and social novelty.
Liu XY, Tao YC, Zhang Q, Liu WT, Zhao L, Hu ZB, Zhou BY, Li ZX, Qi CC, Zhang L, Chen JY, Song NN, Ding YQ
Nr4a2 is critical for the proper development and function of neurons in the subiculum, a key part of the hippocampus involved in memory and social behavior. Without Nr4a2, these neurons lose their identity, fail to connect correctly with other brain regions, and mice show impaired social novelty recognition.
- Nr4a2 maintains subiculum neuron identity
- Loss of Nr4a2 disrupts brain circuit connections
- Nr4a2 deficiency causes social novelty deficits
- Nr4a2 directly controls key gene expression
- Findings link Nr4a2 to hippocampal-related disorders
Dual Nurr1/RXR agonism of valerenic acid and synthetic mimetics enables dimer-selective Nurr1 modulation.
Scholz K, López-García Ú, Busch R, Marschner JA, Merk D
Valerenic acid and similar compounds can selectively activate Nurr1 when it pairs with RXR, which may help treat NR4A2-related conditions by targeting specific gene pathways without disrupting other Nurr1 functions.
- Dual Nurr1/RXR activators target only the Nurr1-RXR heterodimer
- This approach preserves beneficial gene activation while blocking harmful homodimer activity
- In neurons, only a subset of Nurr1 genes were turned on, showing selectivity
- Valerenic acid and synthetic mimetics show promise for precise Nurr1 modulation
- This strategy could lead to safer, more effective treatments for NR4A2-related disorders
Monogenic defects in Russian children with autism spectrum disorders.
Suspitsin EN, Malysheva KS, Laptiev SA, Sharonova OS, Abuzova AS, Kuznitsyna AA, Melashenko TV, Efremova OV, Korzun PR, Binnatova JO, Gorgul YA, Syomina MV, Imyanitov EN
This study found that about 11% of Russian children with autism spectrum disorder have a known monogenic cause, including rare variants in genes like NR4A2, which are linked to neurodevelopmental conditions. Some children had variants in genes associated with syndromes that include autism, intellectual disability, and developmental delay.
- 11% of children had pathogenic variants in known ASD genes
- NR4A2 was among genes with rare variants found in multiple patients
- Variants in NR4A2 and other genes may explain autism and developmental delays
- Exome sequencing effectively identified genetic causes in this cohort
- Findings support genetic testing for children with autism and ID
Single-cell multi-omic landscape reveals anatomical-specific immune features in adult and pediatric sepsis.
Ye Q, Lai X, Liu Y, Zhang Z, Fu Y, Luo J, Liu C, Duan J, Ding H, Liu Y, Ao Z, Tao Y, Ai S, Huang W, Jiang L, Liu Y, Xu F, Cao J
NR4A2 is a key gene in immune cells that worsens sepsis outcomes when overactive, especially in abdominal, lung, and skin infections. Blocking NR4A2 may improve survival, suggesting a potential treatment target for severe infections.
- NR4A2+ T cells are linked to worse sepsis outcomes
- Reducing NR4A2 activity improves survival in sepsis
- NR4A2 overexpression harms recovery
- Immune responses vary by infection site and age
- NR4A2 is a promising target for sepsis therapy
Midnight darkness and evening melatonin pre-treatment reverse night-light-induced neurobehavioural disruptions in a diurnal corvid.
Buniyaadi A, Prabhat A, Bhardwaj SK, Kumar V
Exposure to dim light at night disrupts sleep, mood, and brain function in birds, but giving melatonin in the evening completely reverses these effects. The study shows melatonin protects brain genes linked to learning and mental health, suggesting it could help children with NR4A2-related disorders who have sleep and cognitive issues.
- Dim light at night harms sleep and brain function
- Melatonin given before night light fully reversed brain and behavior problems
- NR4A2 gene expression was disrupted by light at night
- Melatonin protected brain genes involved in learning and mood
- Evening melatonin may help children with NR4A2-related conditions
Similarities of neocortical deep layer Oprk1-positive neurons and claustrum neurons in connectivity and activity.
Fang C, Zhou H, Brecht M, Wang H, Naumann RK
Neurons in the deep layers of the cortex that resemble claustrum neurons in gene expression are connected to sensory areas of the brain and respond similarly to environmental changes and anesthesia, suggesting they form a parallel circuit to the claustrum that may influence brain coordination and behavior.
- Some deep cortical neurons share genes with claustrum neurons
- These neurons connect mainly to sensory brain regions
- They activate in new environments and during anesthesia
- They likely form a parallel circuit to the claustrum
- May influence brain states like sleep and seizures
The Nuclear Receptor Nurr1 Modulates the Expression and Activity of PPARγ in Human Pro-Inflammatory Macrophages.
Santana-Cisneros E, Solís-Barbosa MA, Segovia-Gamboa NC, Meraz-Ríos MA, González-Domínguez E, Hernández-Rivas R, Marrero-Rodríguez D, Sanchez-Torres C
Nurr1 boosts the activity of PPARγ in human immune cells called macrophages by stabilizing the PPARγ protein and reducing a modification that turns it off. This suggests Nurr1 helps control inflammation and may influence other pathways linked to PPARγ, such as metabolism and immune responses.
- Nurr1 increases PPARγ activity in human macrophages
- Nurr1 stabilizes PPARγ protein and reduces its inactivation
- Activating Nurr1 reduces inflammation in pro-inflammatory macrophages
- Nurr1 and PPARγ work together to regulate immune and metabolic genes
- This interaction may offer new treatment strategies for inflammatory conditions
Molecular Characterization of Hypothalamic-Pituitary-Ovarian Axis Regulation in the Manchurian Zokor (Myospalax psilurus) During Seasonal Estrus.
Nai R, Li X, Shan D, Bao S, Wang F, Lin Y, Zhang Y, Hu B, Xie Y, Man D
This study identifies key genes and pathways involved in seasonal breeding in a subterranean rodent, including NR4A2 in the pituitary, which may help explain how reproductive cycles are regulated in the absence of light. The findings highlight the neuroactive ligand-receptor interaction pathway as central to reproductive control across the hypothalamus, pituitary, and ovary.
- NR4A2 is a key gene in the pituitary during seasonal breeding
- The neuroactive ligand-receptor pathway is central to reproductive regulation
- Findings reveal how reproduction is controlled in perpetual darkness
- Gene expression changes differ across hypothalamus, pituitary, and ovary
- Results may inform understanding of human reproductive disorders
Genetic and Environmental Risk Factors for Autism Spectrum Disorder in Saudi Arabia: A Systematic Review.
Hamed NF, Alqahtani AM, Alshaibani F, Elsharif SM, Alamri SAS, Serhan A
Children with NR4A2-related syndrome may have developmental delays, movement issues, and autism-like symptoms due to mutations in the NR4A2 gene, which plays a key role in brain development and function. The condition is often linked to consanguinity and may be influenced by environmental factors like prenatal exposure to phthalates and vitamin D deficiency.
- NR4A2 loss-of-function variants are linked to autism and neurodevelopmental issues
- Consanguinity increases the risk of recessive NR4A2 mutations
- Prenatal phthalate exposure and vitamin D deficiency may worsen outcomes
- NR4A2 is involved in brain development and dopamine regulation
- Environmental and genetic factors interact in complex ways
Early α-Synuclein Pathology Induces Neuroinflammation and Decreases Topoisomerase IIβ Expression in A53T Mice.
Yeman-Kıyak B, Yurdakul T, Selim A, Elibol B, Avşar T, Neğiş Y, Sürmen MG, Şeyhali-Abutayeh R, Akbayır R, Eren MC, Öz P, Çevreli B, Işık S
Early-stage Parkinson's disease in mice with a mutant α-synuclein gene shows brain inflammation and a drop in two important proteins, Nurr1 and Topoisomerase IIβ, which may help explain how the disease starts. These changes appear before major symptoms, suggesting they could be early warning signs or targets for treatment.
- Early α-synuclein buildup triggers brain inflammation in mice
- Nurr1 and Topoisomerase IIβ drop early in disease
- Low Nurr1 and inflammation may drive early Parkinson’s changes
- Topoisomerase IIβ could be a new treatment target
Tanshinone IIA ameliorates pancreatic injury in type 2 diabetic mice by modulating inflammation and endoplasmic reticulum stress via the IL-6/JAK2/STAT3 pathway.
Li Y, Wang D, Liu Y, Liu C, Chen M, Li J, Wu Z, Wu N
Tanshinone IIA reduces pancreatic damage in type 2 diabetes mice by calming inflammation and easing cellular stress through the IL-6/JAK2/STAT3 pathway, with NR4A2 identified as a key target.
- TanIIA protects pancreatic beta cells in diabetic mice
- NR4A2 is a core target with strong binding to TanIIA
- TanIIA reduces inflammation and endoplasmic reticulum stress
- The IL-6/JAK2/STAT3 pathway is central to TanIIA's effect
- TanIIA improves insulin function and reduces cell death
Regulation of NR4A2 Gene Expression and Its Importance in Neurodegenerative and Psychiatric Diseases.
Ruiz-Sánchez E, Rojas C, Yescas Gómez P, Martínez-Rodríguez N, Ruiz-Chow ÁA, Nava-Ruiz C, Ibáñéz-Cervantes G, Arciniega-Martínez IM, Reséndiz-Albor AA, Rojas P
NR4A2 is a critical gene for brain health, and low levels of its activity are linked to Parkinson's, Alzheimer's, schizophrenia, and other brain disorders. The gene is controlled by epigenetic mechanisms like DNA methylation and microRNAs, which may serve as targets for future treatments.
- NR4A2 supports brain development and function
- Low NR4A2 levels are tied to Parkinson's and schizophrenia
- Epigenetic changes regulate NR4A2 expression
- These mechanisms could become treatment targets
- NR4A2 may help detect or treat brain disorders
Combined molecular characterization and dopa-responsive treatment in two patients with NR4A2-associated intellectual developmental disorder.
Liang N, Li T, Deng Y
Two children with NR4A2 gene mutations showed significant improvement in speech and movement after starting levodopa treatment, confirming that dopa-responsive therapy can help some children with this rare genetic condition. The study shows that genetic testing combined with functional analysis can identify treatable cases.
- Levodopa improves speech and motor skills in some NR4A2 children
- Genetic testing with RNA analysis helps confirm treatable mutations
- NR4A2-related disorders can respond to dopaminergic therapy
- Early diagnosis enables targeted treatment
- Clinical improvement seen in both patients after treatment
Nr4a2, A Key Factor Controlling the Development and Functional Maintenance of Forebrain Car3 Neurons.
Tao YC, Zhao L, Zhang Q, Liu XY, Liu WT, Li ZX, Hu L, Zhang L, Chen JY, Ding YQ, Song NN
NR4A2 is essential for the development and ongoing function of a specific group of neurons in the forebrain called Car3 neurons, which are involved in regulating behavior. Without NR4A2, these neurons do not form properly and mice show hyperactivity and reduced anxiety, suggesting NR4A2 plays a critical role in brain circuits linked to movement and emotion.
- NR4A2 controls development and function of forebrain Car3 neurons
- Loss of NR4A2 causes hyperactivity and less anxiety in mice
- Car3 neurons share a common gene profile when NR4A2 is missing
- NR4A2 misexpression turns on Car3-specific genes
- NR4A2 is vital for proper brain circuit formation
Comprehensive Analysis of N6-Methyladenosine Methylation in Transverse Aortic Constriction-Induced Cardiac Fibrosis Based on MeRIP-Seq Analysis.
Liu S, Zhao P, He Y, Wang J, Song B, Yu C
This study found that m6A methylation increases in mouse hearts after pressure overload, driving cardiac fibrosis by altering key genes. The gene NR4A2 was identified as a hub gene in a network linked to fibrosis, suggesting it may play a role in heart disease. These findings point to m6A regulation as a potential target for treating heart fibrosis.
- m6A methylation increases in heart fibrosis
- NR4A2 is a key hub gene in fibrosis-related networks
- m6A changes affect genes involved in heart disease
- Potential drug targets identified through gene networks
- Findings may lead to new treatments for heart fibrosis