Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 Reveals Distinct Signalling Roles Related to Antigen Presentation and Viral Response.
Phelan DE, Shigemura M, Aldhafiri S, Mota C, Hall TJ, Sznajder JI, Murphy EP, Crean D, Cummins EP
NR4A2 and NR4A3 play distinct roles in immune cells called monocytes: NR4A2 helps control how the body presents antigens, which is important for immune responses, while NR4A3 is more involved in fighting viruses. These receptors also influence cell movement and affect gene activity even without immune triggers.
- NR4A2 regulates antigen presentation and MHC genes
- NR4A3 is linked to viral response pathways
- Both receptors affect cell migration
- NR4A2 and NR4A3 have unique roles in immune cells
- Their activity impacts gene expression even at rest
Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1.
Kholodar SA, Lang G, Cortopassi WA, Iizuka Y, Brah HS, Jacobson MP, England PM
A stable chemical analog of a natural dopamine byproduct can activate Nurr1, a key protein for dopamine neuron health, potentially offering a new path to treat conditions like Parkinson's and NR4A2-related syndromes.
- A stable analog activates Nurr1, the protein missing in NR4A2-related syndrome
- Activating Nurr1 boosts dopamine production and packaging genes
- This analog could be a foundation for future therapies
- Directly targets the core biological defect in NR4A2-related disorders
Efficient generation of dopaminergic induced neuronal cells with midbrain characteristics.
Ng YH, Chanda S, Janas JA, Yang N, Kokubu Y, Südhof TC, Wernig M
Researchers developed a method to efficiently create midbrain-like dopamine-producing neurons from stem cells using a combination of specific transcription factors, including Nurr1, which is directly linked to NR4A2-related syndrome. This approach produces more accurate and functional neurons than previous methods, offering potential for modeling and treating neurological conditions.
- Combining Nurr1 with other factors creates midbrain dopamine neurons
- This method improves accuracy and efficiency over older techniques
- Findings may help model NR4A2-related neurological disorders
- Potential for developing future therapies using these neurons
NR4A2 and Dystonia with Dopa Responsiveness.
Winter B, Krämer J, Meinhardt T, Berner D, Alt K, Wenzel M, Winkelmann J, Zech M
NR4A2 mutations cause a rare neurological disorder characterized by dystonia that improves with dopamine treatment. The gene plays a critical role in brain development and dopamine regulation.
- NR4A2 mutations lead to dystonia that responds to dopamine
- The condition is linked to impaired dopamine signaling
- NR4A2 is essential for proper brain development
- Treatment with levodopa can significantly improve symptoms
Matrigel enhances differentiation of human adipose tissue-derived stem cells into dopaminergic neuron.
Absalan F, Pasandi MS, Ghasemi Hamidabadi H, Saeednia S, Bojnordi MN, Zahiri M, Alizadeh R, Bagher Z
Human stem cells from fat can be guided into becoming dopamine-producing neurons more effectively when grown on a special gel called Matrigel, which supports better cell survival and higher dopamine production compared to standard plastic dishes.
- Matrigel improves stem cell growth and neuron formation
- More dopamine-producing cells form on Matrigel than on plastic
- Key brain neuron genes increase during differentiation
- Stem cells from fat show strong potential for Parkinson's research
- This method may help develop future cell-based therapies
Inhibition of miR-145-5p Reduces Spinal Cord Injury-Induced Inflammatory and Oxidative Stress Responses via Affecting Nurr1-TNF-α Signaling Axis.
Jiang L, Wei ZC, Xu LL, Yu SY, Li C
Blocking miR-145-5p reduces inflammation and oxidative stress after spinal cord injury by boosting Nurr1, which in turn suppresses TNF-α signaling. This suggests a potential therapeutic strategy for spinal cord injury involving the NR4A2/Nurr1 pathway.
- miR-145-5p is increased after spinal cord injury
- Nurr1 is suppressed in injury and targeted by miR-145-5p
- Inhibiting miR-145-5p boosts Nurr1 and reduces inflammation
- This pathway controls TNF-α, a key driver of damage
- Targeting miR-145-5p may protect spinal cord tissue
Nurr1 downregulation is caused by CREB inactivation in a Parkinson's disease mouse model.
Xu X, He X, Ma S, Li M, Huang Q
In a mouse model of Parkinson's disease, the drop in Nurr1 levels—critical for dopamine neuron survival—is caused by the inactivation of the CREB protein. Restoring CREB activity boosted Nurr1 and protected dopamine neurons, suggesting a potential new treatment strategy.
- CREB inactivation reduces Nurr1 in Parkinson's mouse models
- Restoring CREB activity increases Nurr1 and protects neurons
- Targeting CREB may help preserve dopamine neurons
- This mechanism could lead to new neuroprotective therapies
LMK235, a small molecule inhibitor of HDAC4/5, protects dopaminergic neurons against neurotoxin- and α-synuclein-induced degeneration in cellular models of Parkinson's disease.
Mazzocchi M, Goulding SR, Wyatt SL, Collins LM, Sullivan AM, O'Keeffe GW
LMK235, a drug that blocks HDAC4 and HDAC5, protects dopamine-producing brain cells from damage in lab models of Parkinson's disease, including from toxins and harmful alpha-synuclein. It boosts neuron growth and survival by activating a key cellular pathway involved in brain development.
- LMK235 protects dopamine neurons from toxin and alpha-synuclein damage
- It enhances neuron growth by boosting a key developmental pathway
- HDAC4/5 inhibition is linked to improved neuron survival in models
- The drug shows promise for slowing Parkinson’s-like degeneration
- Effects were seen in both human and rat brain cells
Intranasal infusion of GD3 and GM1 gangliosides downregulates alpha-synuclein and controls tyrosine hydroxylase gene in a PD model mouse.
Itokazu Y, Fuchigami T, Morgan JC, Yu RK
Intranasal delivery of gangliosides GD3 and GM1 reduces toxic alpha-synuclein levels and helps restore dopamine-producing neurons in a mouse model of Parkinson’s disease by activating the Nurr1 protein and improving gene function in the brain.
- Gangliosides reduce harmful alpha-synuclein buildup
- GM1 boosts tyrosine hydroxylase, a key dopamine enzyme
- Nurr1 (NR4A2) is restored and helps repair neuron function
- Gangliosides act through epigenetic changes in brain cells
- Intranasal delivery reaches the brain effectively
The molecular and epigenetic mechanisms of innate lymphoid cell (ILC) memory and its relevance for asthma.
Verma M, Michalec L, Sripada A, McKay J, Sirohi K, Verma D, Sheth D, Martin R, Dyjack N, Seibold MA, Knapp JR, Tu TH, O'Connor BP, Gorska MM, Alam R
Memory-like innate lymphoid cells (ILC2s) in the lungs can drive asthma-like reactions after repeated allergen exposure, with NR4A2 playing a key role in regulating a gene program that maintains this memory. These cells retain a heightened state of readiness through a balance between repressor and preparedness genes, allowing rapid response to small allergen triggers.
- Memory ILC2s cause asthma-like reactions after mild allergen exposure
- NR4A2 helps control a gene program that maintains ILC2 memory
- A balance between repressor and preparedness genes sustains memory
- Memory can be triggered by small allergen doses due to pre-activated pathways
- Targeting this balance may offer new asthma treatments
Nurr1 deficiency shortens free running period, enhances photoentrainment to phase advance, and disrupts circadian cycling of the dopamine neuron phenotype.
Partington HS, Nutter JM, Eells JB
Nurr1 deficiency in mice leads to shorter free-running rhythms, faster adaptation to light schedule shifts, and loss of daily changes in dopamine neuron numbers, showing that Nurr1 is essential for normal circadian control of dopamine function.
- Nurr1 deficiency shortens the internal circadian rhythm
- Mice with Nurr1 deficiency adapt faster to earlier light cycles
- Dopamine neurons no longer show daily fluctuations in number
- Fewer dopamine neurons at peak activity time in Nurr1-deficient mice
- Nurr1 is critical for circadian regulation of dopamine neurons
Controlling for activity-dependent genes and behavioral states is critical for determining brain relationships within and across species.
Biegler MT, Cantin LJ, Scarano DL, Jarvis ED
NR4A2 expression in bird brains changes with behavior and brain activity, making it unreliable for determining brain structure similarities between birds and mammals. This challenges previous claims about avian brain regions being homologous to mammalian claustrum or insula. Controlling for behavior is essential when using gene expression to compare brains across species.
- NR4A2 is activity-dependent, not stable
- Expression varies with behavior in birds
- Cannot reliably define brain homology
- Previous homology claims may be flawed
- Behavioral state must be controlled in studies
Implantation of human olfactory ecto-mesenchymal stem cells restores locomotion in a rat model of Parkinson's disease.
Farhadi M, Boroujeni ME, Kamrava SK, Bagher Z, Tehrani AM, Aghajanpour F, Ezi S, Soltani R, Khatmi A, Alizadeh R
Human olfactory stem cells improved movement and increased dopamine-related proteins in rats with Parkinson's-like brain damage, suggesting they could help replace lost brain cells in Parkinson's disease.
- Stem cells from the nose improved movement in Parkinson's rats
- Cells boosted levels of key dopamine proteins
- No pre-differentiation needed before transplant
- Results support stem cell therapy for Parkinson's
- Findings may inform future human treatments
Quantitative Immunohistochemistry to Measure Regional Expression of Nurr1 in the Brain and the Effect of the Nurr1 Heterozygous Genotype.
Kummari E, Guo-Ross SX, Partington HS, Nutter JM, Eells JB
Nurr1 protein levels vary widely across brain regions, with the highest expression in sensory and association cortices, and lower levels in dopamine-producing areas and hippocampus. In mice with one missing Nurr1 gene copy, protein levels dropped significantly in most brain regions, but some areas showed compensatory mechanisms. Seizures temporarily increased Nurr1 in the dentate gyrus, suggesting dynamic regulation.
- Nurr1 is highest in sensory and association cortices
- One Nurr1 gene copy loss reduces protein by 20–50% in key brain areas
- Some brain regions compensate for reduced Nurr1
- Seizures cause a short-term spike in Nurr1 in the hippocampus
- Nurr1 levels are linked to brain function and disease
DNA Methylation of the Angiotensinogen Gene, AGT, and the Aldosterone Synthase Gene, CYP11B2 in Cardiovascular Diseases.
Takeda Y, Demura M, Yoneda T, Takeda Y
This study shows that epigenetic changes, specifically DNA methylation, regulate key genes involved in blood pressure control—AGT and CYP11B2—and that these changes are linked to hypertension and heart disease. Low methylation at specific sites increases gene activity, especially under high salt or high aldosterone conditions, contributing to cardiovascular problems.
- DNA methylation normally turns off AGT and CYP11B2 genes
- Low methylation at CEBP sites boosts AGT in heart and fat tissue
- High salt and aldosterone reduce methylation, increasing gene activity
- NR4A2 (NURR1) binding is blocked by methylation of its recognition sites
- Epigenetic changes in these genes are seen in human heart disease
Pramipexole attenuates 6-OHDA-induced Parkinson's disease by mediating the Nurr1/NF-κB pathway.
Gao H, Wang D, Wang YL, Mao JP, Jiang S, Yang XL
Pramipexole improves motor symptoms and protects dopamine neurons in a rat model of Parkinson's disease by reducing brain inflammation and boosting Nurr1, a key protein linked to NR4A2-related disorders.
- Pramipexole reduces brain inflammation and protects dopamine neurons
- It increases Nurr1 levels, which are deficient in NR4A2-related conditions
- Pramipexole lowers harmful proteins like alpha-synuclein and NF-κB
- These effects suggest a potential therapeutic path for NR4A2-related syndromes
- Findings are based on a Parkinson’s disease model with strong biological relevance
Magnetic Targeting of Human Olfactory Mucosa Stem Cells Following Intranasal Administration: a Novel Approach to Parkinson's Disease Treatment.
Simorgh S, Bagher Z, Farhadi M, Kamrava SK, Boroujeni ME, Namjoo Z, Hour FQ, Moradi S, Alizadeh R
This study shows that magnetically guided olfactory stem cells delivered through the nose can improve motor symptoms in rat models of Parkinson's disease by increasing the number of cells reaching the brain and boosting the function of dopamine-producing neurons.
- Magnetic targeting boosts stem cell delivery to the brain
- Intranasal stem cell therapy improved motor symptoms
- Stem cells increased dopamine neuron function
- Nurr1, DAT, and TH levels rose after treatment
- MRI confirmed higher cell accumulation in the brain
Dibutyl phthalate disrupts conserved circadian rhythm in Drosophila and human cells.
Liu W, Cao H, Liao S, Kudłak B, Williams MJ, Schiöth HB
Dibutyl phthalate (DBP) disrupts circadian rhythms in both fruit flies and human cells by altering key genes involved in daily biological timing, including NR4A2 (called Hr38 in flies), which is linked to the neurodevelopmental disorder NR4A2-related syndrome. This disruption occurs at low doses that also increase cell movement and growth, suggesting potential impacts on brain development and function.
- DBP disrupts circadian rhythms in flies and human cells
- NR4A2 (Hr38) gene expression is altered by DBP
- Circadian disruption occurs at low, environmentally relevant doses
- DBP increases cell migration and proliferation
- Findings may explain broader health effects of phthalates
Correction to Assessment of NR4A Ligands That Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1.
Munoz-Tello P, Lin H, Khan P, de Vera IMS, Kamenecka TM, Kojetin DJ
This paper corrects earlier findings about compounds that bind to and affect Nurr1, a protein linked to NR4A2-related syndrome. It identifies specific molecules that directly interact with Nurr1, which may help develop treatments for related neurological conditions.
- Identifies direct Nurr1-binding compounds
- Corrects previous mischaracterizations of ligand activity
- Potential for developing targeted therapies
- Relevance to NR4A2/Nurr1-related disorders
Caveolin-1 downregulation promotes the dopaminergic neuron-like differentiation of human adipose-derived mesenchymal stem cells.
Han C, Wang YJ, Wang YC, Guan X, Wang L, Shen LM, Zou W, Liu J
Lowering caveolin-1 levels helps human fat stem cells turn into dopamine-producing neurons, suggesting caveolin-1 blocks this process and could be a target for future therapies.
- Caveolin-1 decreases during dopamine neuron formation
- Reducing caveolin-1 boosts dopamine neuron development
- Key dopamine markers increase when caveolin-1 is lowered
- This suggests caveolin-1 acts as a brake on neuron differentiation
- Could inform future treatments for dopamine-related disorders
NF‑κB is negatively associated with Nurr1 to reduce the inflammatory response in Parkinson's disease.
Gao H, Wang D, Jiang S, Mao J, Yang X
In Parkinson's disease, reducing NF-κB activity boosts Nurr1 levels, which helps lower brain inflammation, protect dopamine-producing neurons, and reduce harmful protein buildup. This suggests that targeting NF-κB could be a promising strategy to slow disease progression.
- NF-κB increases inflammation in Parkinson’s disease
- Nurr1 protects brain cells and reduces inflammation
- Blocking NF-κB raises Nurr1 levels and improves neuron health
- Lowering NF-κB may help slow Parkinson’s progression
- This pathway could be a target for future treatments
DNA methylation and exposure to violence among African American young adult males.
Saadatmand F, Gurdziel K, Jackson L, Kwabi-Addo B, Ruden DM
Exposure to violence in young African American males is linked to changes in DNA methylation in genes related to the nervous and immune systems, with specific genes like NR4A2 showing altered methylation patterns that may affect brain and immune function.
- Violence exposure alters DNA methylation in nervous and immune system genes
- NR4A2 methylation changes were observed in relation to violence exposure
- These changes may affect brain and immune function long-term
- Findings highlight potential biological impacts of trauma in young males
- Epigenetic changes could contribute to future health risks
A single-cell survey of the human glomerulonephritis.
Chen Z, Zhang T, Mao K, Shao X, Xu Y, Zhu M, Zhou H, Wang Q, Li Z, Xie Y, Yuan X, Ying L, Zhang M, Hu J, Mou S
This study used single-cell analysis to map immune and kidney cell changes in human glomerulonephritis, identifying specific cell types and genes linked to diseases like IgA nephropathy, membranous nephropathy, and lupus nephritis, including the gene NR4A2 in membranous nephropathy.
- NR4A2 is highly expressed in membranous nephropathy at the cellular level
- Immune cell infiltration and interferon signaling are key in lupus nephritis
- Podocyte and mesangial cell changes are linked to specific glomerulonephritis types
- Single-cell data reveals disease-specific gene markers for potential diagnostics
- Findings may guide future targeted therapies for kidney diseases
microRNAs (miR 9, 124, 155 and 224) transdifferentiate mouse macrophages to neurons.
Challagundla N, Agrawal-Rajput R
MicroRNAs can directly convert mouse macrophages into functional neurons without using transcription factors, offering a potential path for repairing brain damage. The process involves temporary stem-like states, changes in cell cycle, and produces neurons that fire electrical signals and form synapses.
- MicroRNAs reprogram macrophages into functional neurons
- No transcription factors or stem cells needed
- Neurons show electrical activity and synaptic connections
- Works on human blood-derived cells too
- Could enable in vivo brain repair without tumors
Impaired neurite development and mitochondrial dysfunction associated with calcium accumulation in dopaminergic neurons differentiated from the dental pulp stem cells of a patient with metatropic dysplasia.
Sun X, Kato H, Sato H, Torio M, Han X, Zhang Y, Hirofuji Y, Kato TA, Sakai Y, Ohga S, Fukumoto S, Masuda K
A mutation in the TRPV4 gene causes abnormal calcium buildup in brain cells derived from a patient with metatropic dysplasia, leading to poor neuron development and mitochondrial problems. These issues likely contribute to the patient's neuropsychiatric symptoms and suggest that targeting mitochondria could help treat brain-related symptoms.
- TRPV4 mutation causes excessive calcium in brain cells
- Neurons show poor growth and damaged mitochondria
- Mitochondrial dysfunction links to low energy and high stress
- Correcting the gene fixed the problems in lab cells
- Mitochondria may be a treatment target for brain symptoms
Exosomal miR-409-3p secreted from activated mast cells promotes microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway.
Hu L, Si L, Dai X, Dong H, Ma Z, Sun Z, Li N, Sha H, Chen Y, Qian Y, Zhang Z
Activated mast cells release exosomes containing miR-409-3p, which enters microglial cells and reduces NR4A2 levels, leading to increased microglial activity, inflammation, and brain cell damage. This process worsens neuroinflammation through the NF-κB pathway.
- Mast cell exosomes carry miR-409-3p that harms brain cells
- miR-409-3p lowers NR4A2, a key brain-protective protein
- This triggers microglial overactivity and brain inflammation
- Blocking this pathway may reduce brain inflammation
- NR4A2 deficiency is central to this harmful process
Fragment-like Chloroquinolineamines Activate the Orphan Nuclear Receptor Nurr1 and Elucidate Activation Mechanisms.
Willems S, Ohrndorf J, Kilu W, Heering J, Merk D
Researchers found small, fragment-like molecules that activate Nurr1, a protein linked to brain health, and showed these molecules boost Nurr1's activity in human cells. These compounds help reveal how Nurr1 works and could lead to new treatments for neurodevelopmental and neurodegenerative conditions.
- New small molecules activate Nurr1, a key protein in brain function.
- These molecules enhance Nurr1 activity in human cells, including astrocytes.
- They help uncover how Nurr1 is turned on and forms protein complexes.
- The findings offer starting points for developing potential therapies.
- These tools are useful for studying Nurr1 in disease models.
Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson's Disease. A Systematic Review.
Kambey PA, Kanwore K, Ayanlaja AA, Nadeem I, Du Y, Buberwa W, Liu W, Gao D
NR4A2 (NURR1) is a key regulator of dopamine neuron development and survival, and its deficiency may explain why GDNF therapy fails in Parkinson's disease clinical trials. Restoring NR4A2 function could enhance the effectiveness of neurotrophic treatments like GDNF.
- NR4A2 controls genes needed for dopamine neuron health
- Low NR4A2 levels may block GDNF's benefits in humans
- Boosting NR4A2 could make GDNF therapy work better
- NR4A2 is a promising target for Parkinson's treatments
The Effects of Selective Inhibition of Histone Deacetylase 1 and 3 in Huntington's Disease Mice.
Hecklau K, Mueller S, Koch SP, Mehkary MH, Kilic B, Harms C, Boehm-Sturm P, Yildirim F
In a mouse model of Huntington's disease, blocking HDAC1 and HDAC3 improved gene expression and motor learning, but did not stop brain shrinkage or affect anxiety and movement. This suggests a potential path to help with some symptoms, though not all.
- HDAC1/3 inhibition improved motor learning in HD mice
- Gene expression changes, including in Nr4a2, were reversed
- No effect on brain atrophy or anxiety-like behavior
- Targeting epigenetics may help specific HD symptoms
- Nr4a2 is a key gene affected by this treatment
PT3: A Novel Benzamide Class Histone Deacetylase 3 Inhibitor Improves Learning and Memory in Novel Object Recognition Mouse Model.
Pulya S, Mahale A, Bobde Y, Routholla G, Patel T, Swati, Biswas S, Sharma V, Kulkarni OP, Ghosh B
PT3, a new brain-penetrating HDAC3 inhibitor, improves memory in mice by boosting levels of key genes involved in learning and memory, including NR4A2. It increases acetylation of histone H3K9 in the hippocampus, which activates memory-related genes. These findings suggest PT3 could help treat memory disorders like Alzheimer's.
- PT3 enhances memory in mice by targeting HDAC3
- It increases NR4A2 and other memory genes in the brain
- PT3 crosses the blood-brain barrier effectively
- It boosts histone acetylation linked to memory formation
- Potential therapy for memory decline and neurodegenerative diseases
Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study.
Ruiz-Sánchez E, Jiménez-Genchi J, Alcántara-Flores YM, Castañeda-González CJ, Aviña-Cervantes CL, Yescas P, Del Socorro González-Valadez M, Martínez-Rodríguez N, Ríos-Ortiz A, González-González M, López-Navarro ME, Rojas P
In people with schizophrenia from a Mexican population, the rs34884856 genetic variant in the NR4A2 gene is linked to working memory performance, especially when the gene's activity level is high. This suggests that how much NR4A2 is turned on may affect thinking skills in some individuals with schizophrenia.
- The rs34884856 variant affects working memory in schizophrenia
- Higher NR4A2 gene activity improves working memory in some patients
- Gene expression matters more in people with a specific genetic variant
- Findings are from a Mexican population sample
- No overall difference in gene levels between patients and controls
Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis.
Crean D, Murphy EP
NR4A receptors, including NR4A2, help control inflammation, metabolism, and blood vessel growth in stromal cells, which are key players in chronic diseases and cancer. The review highlights how these receptors influence immune responses and tissue changes in conditions like rheumatoid arthritis and tumor development.
- NR4A2 helps regulate immune and inflammatory responses in stromal cells
- NR4A receptors influence tissue damage and repair in chronic inflammation
- Targeting NR4A receptors may affect tumor growth by altering the tumor environment
- NR4A2 is involved in controlling cell behavior linked to disease progression
Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology.
Odagiu L, May J, Boulet S, Baldwin TA, Labrecque N
NR4A2 is a key regulator in T-cell development and function, influencing how immune cells respond to infections and cancer. These receptors are rapidly activated in T cells after immune stimulation and control immune responses without needing external signals.
- NR4A2 helps shape T-cell development in the thymus
- It activates quickly when T cells detect threats
- NR4A2 regulates immune responses without needing a ligand
- It plays a role in fighting infections and cancer
- Its activity depends on how much is produced, not external triggers
Attenuated macrophage activation mediated by microRNA-183 knockdown through targeting NR4A2.
Gong FH, Long L, Yang YS, Shen DH, Zhang YS, Wang XS, Zhang XP, Xiao XQ
Blocking miR-183 reduces harmful inflammation in immune cells by increasing NR4A2, a gene linked to NR4A2-related syndrome, suggesting a potential treatment path for related conditions.
- miR-183 blocks NR4A2, worsening inflammation
- Lowering miR-183 boosts NR4A2 and reduces inflammation
- This shift may help repair immune function in NR4A2-related syndrome
- Findings suggest miR-183 could be a treatment target
The orphan nuclear receptor Nurr1 agonist amodiaquine mediates neuroprotective effects in 6-OHDA Parkinson's disease animal model by enhancing the phosphorylation of P38 mitogen-activated kinase but not PI3K/AKT signaling pathway.
Kambey PA, Chengcheng M, Xiaoxiao G, Abdulrahman AA, Kanwore K, Nadeem I, Jiao W, Gao D
A drug called amodiaquine activates the Nurr1 protein, which protects dopamine-producing brain cells in a mouse model of Parkinson's disease. It works by boosting a specific signaling pathway (P38 MAPK) that supports neuron survival, without affecting another common protective pathway (PI3K/AKT).
- Amodiaquine activates Nurr1, protecting brain cells in Parkinson's models
- It works through P38 MAPK signaling, not PI3K/AKT
- Boosts levels of tyrosine hydroxylase, a key dopamine enzyme
- May help preserve motor function in Parkinson's-like conditions
- Offers a potential therapeutic path for NR4A2-related disorders
Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1.
Jang Y, Kim W, Leblanc P, Kim CH, Kim KS
New synthetic and natural compounds can bind to Nurr1, a protein linked to NR4A2-related syndrome, and may help treat neurological and inflammatory conditions by activating this protein.
- Nurr1 can be activated by specific synthetic and natural compounds.
- These ligands change Nurr1's shape to make it functional.
- Activating Nurr1 may help treat symptoms of NR4A2-related syndrome.
- This opens potential for new treatments targeting Nurr1 directly.
- Findings are based on detailed structural studies of Nurr1.
NR4A2 Mutations Can Cause Intellectual Disability and Language Impairment With Persistent Dystonia-Parkinsonism.
Jesús S, Hinarejos I, Carrillo F, Martínez-Rubio D, Macías-García D, Sánchez-Monteagudo A, Adarmes A, Lupo V, Pérez-Dueñas B, Mir P, Espinós C
NR4A2 gene mutations cause a rare neurodevelopmental disorder featuring intellectual disability, language delays, and a movement disorder that includes dystonia and parkinsonism, which persists into adulthood.
- NR4A2 mutations lead to intellectual disability and language issues
- Persistent dystonia and parkinsonism are key movement symptoms
- Symptoms start early and continue into adulthood
- NR4A2 is critical for brain development and motor control
- Findings support NR4A2-related syndrome as a distinct clinical entity