Predicting functional regulatory SNPs in the human antimicrobial peptide genes DEFB1 and CAMP in tuberculosis and HIV/AIDS.
Flores Saiffe Farías A, Jaime Herrera López E, Moreno Vázquez CJ, Li W, Prado Montes de Oca E
This study developed a new computational method to predict which genetic variations in antimicrobial peptide genes may affect gene activity in tuberculosis and HIV/AIDS. It identified specific DNA changes that likely alter how transcription factors bind, including NR4A2, which is relevant to neurodevelopmental conditions like NR4A2-related syndrome.
- Identified 10 SNPs affecting transcription factor binding in key immune genes
- NR4A2 is among TFs predicted to be impacted by these SNPs
- Method improves accuracy by including chromatin and redundancy data
- Algorithm shows promise for finding functional genetic variants
- Could help identify drug targets for complex diseases
Nurr1 reduction influences the onset of chronic EAE in mice.
Montarolo F, Perga S, Martire S, Bertolotto A
Reducing Nurr1 levels in mice leads to earlier onset of a multiple sclerosis-like disease and more inflammation in the spinal cord, suggesting Nurr1 helps control early immune activity in the nervous system.
- Nurr1 reduction speeds up MS-like disease in mice
- Less Nurr1 means more brain and spinal cord inflammation
- Nurr1 may help calm immune responses in the nervous system
- Lower Nurr1 levels in MS patients link to worse disease
Animal models of Parkinson's disease: An updated overview.
Gubellini P, Kachidian P
This paper reviews animal models of Parkinson's disease, including both toxin-based and genetic models that mimic human PD features. While it mentions Nurr1 (NR4A2) as one of the genes used to create models, the focus is on general PD research, not on NR4A2-related syndrome specifically.
- NR4A2 (Nurr1) is used in some genetic PD models
- Models help study PD causes and test treatments
- Toxin and genetic models each have strengths and limits
- No direct focus on NR4A2-related syndrome
- Relevance to rare genetic disorders is indirect
Facilitated Neural Differentiation of Adipose Tissue-Derived Stem Cells by Electrical Stimulation and Nurr-1 Gene Transduction.
Yang Y, Ma T, Ge J, Quan X, Yang L, Zhu S, Huang L, Liu Z, Liu L, Geng D, Huang J, Luo Z
Combining electrical stimulation with Nurr-1 gene delivery significantly improves the ability of fat-derived stem cells to become neuron-like cells, especially those that produce dopamine, which may help treat brain disorders like Parkinson’s.
- Electrical stimulation at 1 V/cm boosts stem cell neuron development
- Adding Nurr-1 gene enhances dopamine production and nerve-like growth
- This combo increases key neuron markers and reduces non-neural cell genes
- Results suggest a potential therapy for brain injuries and neurodegenerative diseases
- Fat stem cells become more effective brain-like cells with this treatment
The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats.
Li YS, He X, Ma K, Wu YP, Li BX
Exposure to the herbicide atrazine during puberty in rats disrupts the development of the brain's dopamine system, reducing dopamine levels and altering genes linked to dopamine neuron health, including Nurr1, which is the same gene affected in NR4A2-related syndrome.
- Atrazine harms dopamine development in pubertal rats
- Reduced dopamine and key genes like Nurr1 were found
- Nurr1 is the same gene mutated in NR4A2-related syndrome
- Early environmental exposure may affect brain development
- Findings suggest environmental toxins could worsen NR4A2-related conditions
Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77.
Leblanc P, Moon M, Kim W, Jeong I, Kim CH, Kim KS
This study developed highly specific antibodies that target Nurr1 (NR4A2) without reacting to its closely related proteins, Nur77 and NOR1. The method uses the most different part of Nurr1 (its ligand-binding domain) to generate antibodies, then removes any cross-reactive ones by filtering through the other proteins.
- Created Nurr1-specific antibodies with no cross-reactivity
- Used the unique ligand-binding domain for precise targeting
- Removed unwanted reactivity using pre-adsorption
- Improves accuracy in studying Nurr1 in brain function
- Helps research into NR4A2-related neurological conditions
Decreased expression levels of Nurr1 are associated with chronic inflammation in patients with type 2 diabetes.
Xu Y, Huang Q, Zhang W, Wang Y, Zeng Q, He C, Xue J, Chen J, Hu X, Xu Y
Lower levels of the Nurr1 protein in immune cells are linked to higher inflammation and insulin resistance in people with type 2 diabetes. High glucose and fat levels reduce Nurr1 expression, suggesting a direct role in disease progression.
- Low Nurr1 levels correlate with inflammation in type 2 diabetes
- High glucose and fat reduce Nurr1 in immune cells
- Nurr1 loss is tied to insulin resistance
- Nurr1 may protect against diabetes-related inflammation
- Nurr1 could be a target for new treatments
Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors.
Giner XC, Cotnoir-White D, Mader S, Lévesque D
This study developed a new method to test how drugs affect specific nuclear receptor pairs, including Nurr1/RXR, which is relevant to NR4A2-related syndrome. It found that one drug, SR11237, strongly activates the Nurr1/RXR complex, suggesting it could be a promising treatment lead. The technique may help discover more precise drugs for NR4A2-related conditions.
- New test detects drug effects on specific nuclear receptor pairs
- SR11237 boosts activity of Nurr1/RXR, a key complex in NR4A2 syndrome
- Method could find better, targeted treatments for NR4A2-related disorders
- Results support exploring SR11237 as a potential therapy
- Technology enables precise drug screening for nuclear receptor dimers
Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells.
Crean D, Cummins EP, Bahar B, Mohan H, McMorrow JP, Murphy EP
Adenosine helps calm excessive inflammation in immune cells by boosting NR4A2, a key regulator that normally keeps NF-κB activity in check. Without NR4A2, immune cells become hyperactive and produce more inflammatory signals, worsening inflammation. This suggests that supporting NR4A2 function could help control harmful inflammation in NR4A2-related conditions.
- NR4A2 reduces inflammation by limiting NF-κB activity
- Loss of NR4A2 leads to stronger inflammatory responses
- Adenosine boosts NR4A2 to calm immune cell overactivity
- NR4A2 helps control genes linked to inflammation
- Targeting this pathway may help treat NR4A2-related inflammation
Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease.
Zhang LM, Sun CC, Mo MS, Cen L, Wei L, Luo FF, Li Y, Li GF, Zhang SY, Yi L, Huang W, Liu ZL, Le WD, Xu PY
Dopamine agonist drugs increase Nurr1 levels in blood cells of Parkinson's patients, suggesting these drugs may protect dopamine neurons by boosting a key protective protein. This effect was seen both in patients taking the drugs and in lab tests with blood cells treated with pramipexole.
- Dopamine agonists raise Nurr1 levels in blood cells
- Higher Nurr1 may protect dopamine neurons
- Pramipexole increased Nurr1 in lab tests
- Both pramipexole and L-dopa boost Nurr1
- Nurr1 in blood may reflect brain protection
Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease.
Kim CH, Han BS, Moon J, Kim DJ, Shin J, Rajan S, Nguyen QT, Sohn M, Kim WG, Han M, Jeong I, Kim KS, Lee EH, Tu Y, Naffin-Olivos JL, Park CH, Ringe D, Yoon HS, Petsko GA, Kim KS
Drugs that activate the Nurr1 protein, which is essential for the development and survival of dopamine-producing brain cells, can improve movement problems in a rat model of Parkinson's disease without causing dyskinesia. These drugs, including two antimalarials, enhance Nurr1's ability to protect brain cells and reduce harmful inflammation. This suggests a promising new strategy for treating Parkinson's by targeting the root cause, not just symptoms.
- Nurr1 activation protects dopamine neurons
- Two antimalarial drugs boost Nurr1 function
- Improved movement without dyskinesia in rats
- Nurr1-targeting drugs may slow Parkinson's progression
- Proof that Nurr1 agonists are neuroprotective
The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells.
Hou Y, Li W, Sheng Y, Li L, Huang Y, Zhang Z, Zhu T, Peace D, Quigley JG, Wu W, Zhao YY, Qian Z
Foxm1 helps keep blood stem cells quiet and healthy by turning on the Nurr1 gene, and low levels of this process may contribute to blood disorders. Restoring Nurr1 can fix problems caused by missing Foxm1, suggesting a potential treatment path.
- Foxm1 keeps blood stem cells in a resting state
- Foxm1 controls the Nurr1 gene
- Low Foxm1 or Nurr1 links to blood disorders
- Boosting Nurr1 fixes stem cell issues
- This pathway may be targeted for therapy
Localization of nuclear receptor subfamily 4, group A, member 3 (NR4A3) in Lewy body disease and multiple system atrophy.
Kon T, Miki Y, Tanji K, Mori F, Tomiyama M, Toyoshima Y, Kakita A, Takahashi H, Utsumi J, Sasaki H, Wakabayashi K
NR4A3 accumulates in abnormal protein clumps in brain and spinal cord tissues from people with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy—conditions linked to alpha-synuclein buildup. The protein was found inside these clumps, which also contained phosphorylated alpha-synuclein, suggesting NR4A3 is specifically involved in alpha-synuclein-related diseases.
- NR4A3 builds up in alpha-synuclein clumps in Parkinson's and related disorders
- NR4A3 co-localizes with phosphorylated alpha-synuclein in disease inclusions
- NR4A3 was not found in clumps from other neurodegenerative diseases
- This suggests NR4A3 is specifically tied to alpha-synucleinopathies
Age-related gene expression changes in substantia nigra dopamine neurons of the rat.
Parkinson GM, Dayas CV, Smith DW
Ageing in rats leads to changes in gene activity in dopamine neurons of the substantia nigra, particularly involving reduced levels of Nurr1, a key protein for dopamine neuron health. These changes likely impair dopamine production and function, contributing to motor decline without significant neuron loss.
- Ageing reduces Nurr1 levels in dopamine neurons
- Gene changes affect dopamine production and neuron function
- Motor decline may stem from neuron dysfunction, not cell death
- Altered neurotrophic signalling may play a role
- Findings mirror early Parkinson’s changes
Microsphere-Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells.
Patel M, Moon HJ, Jung BK, Jeong B
This study shows that a 3D gel system releasing growth factors can effectively turn tonsil-derived stem cells into neuron-like cells, with strong activation of Nurr-1, a key protein linked to NR4A2-related syndrome. The system mimics brain tissue stiffness and supports long-term growth factor delivery, which may help repair nervous system damage.
- Stem cells turned into neuron-like cells using a 3D gel system
- Nurr-1, a protein tied to NR4A2 syndrome, was strongly activated
- Growth factors released slowly over 12–18 days
- Gel stiffness matches brain tissue, supporting cell growth
- Potential for treating neurological conditions using stem cells
Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage.
Lim MS, Chang MY, Kim SM, Yi SH, Suh-Kim H, Jung SJ, Kim MJ, Kim JH, Lee YS, Lee SY, Kim DW, Lee SH, Park CH
Scientists turned mouse skin cells into expandable neural precursor cells that can be guided into midbrain dopamine neurons, the type lost in Parkinson's disease. These cells can be grown for many generations and, when given specific genes, become functional dopamine neurons capable of potentially treating Parkinson's in animal models.
- Skin cells were reprogrammed into expandable neural precursor cells
- These cells can be grown for over 100 generations
- Adding Nurr1 and Foxa2 genes turned them into dopamine neurons
- The dopamine neurons showed key functions needed for brain circuits
- The approach shows promise for treating Parkinson's in animal models
Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.
Chandra R, Francis TC, Konkalmatt P, Amgalan A, Gancarz AM, Dietz DM, Lobo MK
Egr3 has opposite effects in two types of brain cells in the reward center: it increases cocaine's effects in one type (D1-MSNs) but reduces them in the other (D2-MSNs). Repeated cocaine changes how Egr3 binds to genes involved in brain plasticity, especially those linked to NR4A2, which is relevant to NR4A2-related syndrome.
- Egr3 boosts cocaine effects in D1 brain cells, reduces them in D2 cells
- Cocaine changes Egr3 binding to key plasticity genes like Nr4a2
- Egr3 regulates genes tied to brain adaptation and behavior
- NR4A2 is among genes affected by Egr3, linking to NR4A2 syndrome
- This suggests Egr3 could be a target for balancing brain cell activity
Nur77 Was Essential for Neurite Outgrowth and Involved in Schwann Cell Differentiation After Sciatic Nerve Injury.
Zhang W, Zhu X, Liu Y, Chen M, Yan S, Mao X, Liu Z, Wu W, Chen C, Xu X, Wang Y
Nur77 plays a key role in nerve repair after injury by promoting the growth of nerve fibers and the development of Schwann cells, which support nerve regeneration. Blocking Nur77 activity significantly reduces both myelin formation and nerve regrowth.
- Nur77 boosts nerve fiber regrowth after injury
- Nur77 helps Schwann cells mature and form myelin
- Reducing Nur77 blocks nerve repair in models
- Nur77 is active in both nerves and Schwann cells
- Targeting Nur77 could improve nerve recovery
Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis.
Mahajan S, Saini A, Chandra V, Nanduri R, Kalra R, Bhagyaraj E, Khatri N, Gupta P
Nr4a2 helps macrophages switch to a protective, anti-inflammatory state that reduces damage in sepsis, and boosting Nr4a2 improves survival in mouse models of severe infection.
- Nr4a2 drives macrophages toward a protective, anti-inflammatory state
- It activates arginase 1, a key marker of this protective macrophage type
- Higher Nr4a2 levels improve survival in sepsis models
- The effect is linked to the PI3K-Akt signaling pathway
- This suggests Nr4a2 could be a target for treating inflammatory conditions
Age-dependent Müller glia neurogenic competence in the mouse retina.
Löffler K, Schäfer P, Völkner M, Holdt T, Karl MO
Mouse Müller glia can be stimulated to re-enter the cell cycle and generate neuron-like cells, but this ability declines with age. The process involves activation of neurogenic genes like Nr4a2 and production of cells that resemble amacrine neurons, though not photoreceptors.
- Müller glia in young mice can become neurogenic after stimulation
- Nr4a2 is activated during reprogramming to neurogenesis
- Regenerative potential decreases as mice age
- Progeny express neuronal markers but not photoreceptor markers
- This model may help overcome limits to retinal repair
Epigenetic regulation contributes to urocortin-enhanced midbrain dopaminergic neuron differentiation.
Huang HY, Chiu TL, Chang HF, Hsu HR, Pang CY, Liew HK, Wang MJ
Urocortin helps drive the development of dopamine-producing brain cells in the midbrain by altering gene activity through epigenetic changes, specifically by removing repressive complexes from key genes and boosting the expression of critical transcription factors like Nurr1. This process enhances the formation of functional dopamine neurons both in lab cultures and in living animals.
- Urocortin boosts dopamine neuron development in the midbrain
- It works by modifying chromatin to activate key genes
- Urocortin removes repressor complexes from the TH gene promoter
- This involves HDAC inhibition and increased Nurr1 activity
- Results seen in both lab cultures and live animal models
Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease.
Oh SM, Chang MY, Song JJ, Rhee YH, Joe EH, Lee HS, Yi SH, Lee SH
Delivering both Nurr1 and Foxa2 genes using viral vectors protects dopamine neurons and improves movement in a Parkinson's disease mouse model, with effects lasting over a year. This combined approach works both inside neurons and by signaling to nearby cells, suggesting a powerful new therapy strategy.
- Nurr1 and Foxa2 protect dopamine neurons from damage
- Delivering both genes together works better than either alone
- Effects lasted over a year in mice
- Works by protecting neurons directly and through nearby glial cells
- Potential therapy for Parkinson's disease
Microdeletion 2q23.3q24.1: exploring genotype-phenotype correlations.
Milani D, Sabatini C, Manzoni FM, Ajmone PF, Rigamonti C, Malacarne M, Pierluigi M, Cavani S, Costantino MA
A 13-year-old girl with a rare 5.4 Mb deletion on chromosome 2 has developmental delay, behavioral issues, and minor physical features. Genes in the deleted region, especially NR4A2, may play a key role in her neurological symptoms.
- Deletion includes NR4A2, a gene linked to brain development
- Behavioral and developmental issues match NR4A2-related syndromes
- Other genes in the region may contribute to neurological symptoms
- This case helps clarify the role of NR4A2 in human neurodevelopment
- Findings support NR4A2 as a likely driver of the phenotype
Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons.
Noisa P, Raivio T, Cui W
This study shows that human embryonic stem cells can be turned into neural progenitor cells and then into midbrain dopaminergic neurons, which are the type of brain cells lost in Parkinson's disease. The resulting neurons express key markers like NURR1, indicating they are the right type for potential therapies.
- Neural progenitor cells from stem cells become midbrain dopaminergic neurons
- Key genes like NURR1 and PITX3 confirm correct neuron identity
- These cells could be used to treat Parkinson's disease
- The process uses known signals like SHH and FGF8
- The method provides a renewable source of therapeutic neurons
Nuclear receptor 4A (NR4A) family - orphans no more.
Safe S, Jin UH, Morpurgo B, Abudayyeh A, Singh M, Tjalkens RB
NR4A2 is a key regulator in brain development and function, and its dysfunction is linked to neurological disorders. Research shows that synthetic molecules can target NR4A2, opening potential for future treatments of NR4A2-related conditions.
- NR4A2 is critical for brain health and development
- Mutations in NR4A2 cause neurological syndromes
- Synthetic drugs can activate or block NR4A2
- Targeting NR4A2 may lead to new therapies
- NR4A2 plays a role in maintaining cellular balance
Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.
Eells JB, Varela-Stokes A, Guo-Ross SX, Kummari E, Smith HM, Cox AD, Lindsay DS
Mice with a partial deficiency in the NR4A2 gene (Nurr1) show worsened hyperactivity and other behavioral changes after a Toxoplasma gondii infection, especially when antibody levels are moderate. This suggests that genetic vulnerability in NR4A2 combined with infection can amplify brain changes linked to schizophrenia-like symptoms. The findings highlight how infections may trigger or worsen neurological symptoms in individuals with NR4A2-related conditions.
- NR4A2 deficiency in mice worsens hyperactivity after Toxoplasma infection
- Infection amplifies dopamine-related behavioral changes in genetically vulnerable mice
- Moderate antibody levels correlate with the greatest behavioral disruption
- This supports a gene-environment interaction in NR4A2-related neurodevelopmental disorders
- Findings may inform risk and management strategies for children with NR4A2 variants
The Nurr1 Activator 1,1-Bis(3'-Indolyl)-1-(p-Chlorophenyl)Methane Blocks Inflammatory Gene Expression in BV-2 Microglial Cells by Inhibiting Nuclear Factor κB.
De Miranda BR, Popichak KA, Hammond SL, Jorgensen BA, Phillips AT, Safe S, Tjalkens RB
The compound C-DIM12 activates Nurr1, a protein linked to NR4A2-related syndrome, to reduce brain inflammation in microglial cells by blocking the activity of a key inflammatory pathway. This suggests a potential treatment strategy to calm harmful brain inflammation in children with NR4A2-related conditions.
- C-DIM12 activates Nurr1 to reduce brain inflammation
- It blocks NF-κB, a major driver of neuroinflammation
- The effect depends on Nurr1 and stabilizes anti-inflammatory proteins
- May help treat inflammation in NR4A2-related neurological disorders
- Found effective in human-like microglial cells
Vitamin C facilitates dopamine neuron differentiation in fetal midbrain through TET1- and JMJD3-dependent epigenetic control manner.
He XB, Kim M, Kim SY, Yi SH, Rhee YH, Kim T, Lee EH, Park CH, Dixit S, Harrison FE, Lee SH
Vitamin C helps brain cells become dopamine neurons by changing how genes are turned on through epigenetic mechanisms. These changes depend on two enzymes, TET1 and JMJD3, and are disrupted when vitamin C is missing. This process is essential for proper development of dopamine neurons in the midbrain.
- Vitamin C boosts dopamine neuron formation in developing brain tissue
- It works by modifying DNA and histone marks via TET1 and JMJD3
- Low vitamin C disrupts dopamine neuron development in mice
- These changes affect gene access needed for dopamine neuron identity
- Svct2 transporter is critical for maintaining vitamin C in the brain
Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells' differentiation in vitro and in neurochemical models of Parkinson's disease.
Carrieri C, Forrest AR, Santoro C, Persichetti F, Carninci P, Zucchelli S, Gustincich S
AS Uchl1, a long non-coding RNA that boosts the production of UCHL1 protein, is controlled by Nurr1—a key factor in dopamine neuron development. Its levels drop in models of Parkinson’s disease, suggesting it may play a role in protecting dopamine neurons.
- AS Uchl1 boosts UCHL1 protein production
- Nurr1 regulates AS Uchl1 expression
- AS Uchl1 levels fall in Parkinson’s models
- AS Uchl1 is part of a protective network in dopamine neurons
A Nurr1 agonist causes neuroprotection in a Parkinson's disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C).
Smith GA, Rocha EM, Rooney T, Barneoud P, McLean JR, Beagan J, Osborn T, Coimbra M, Luo Y, Hallett PJ, Isacson O
A drug that activates the Nurr1 protein protects dopamine-producing brain cells in a model of Parkinson's disease that includes inflammation. The drug reduced harmful brain immune activity and helped preserve nerve fibers, suggesting it could be a promising treatment for conditions like NR4A2-related syndrome.
- Nurr1 activation protects brain cells from degeneration
- Drug reduces harmful brain inflammation
- Improves nerve fiber survival in a Parkinson's model
- Targets both neuron health and immune response
- Supports Nurr1 as a potential treatment target
NR4A receptors up-regulate the antiproteinase alpha-2 macroglobulin (A2M) and modulate MMP-2 and MMP-9 in vascular smooth muscle cells.
Rodríguez-Calvo R, Ferrán B, Alonso J, Martí-Pàmies I, Aguiló S, Calvayrac O, Rodríguez C, Martínez-González J
NR4A receptors in blood vessel cells increase production of a protein called alpha-2 macroglobulin (A2M), which helps block enzymes that break down tissue. This process reduces activity of two key enzymes (MMP-2 and MMP-9) involved in tissue remodeling, potentially protecting blood vessels. The findings suggest NR4A receptors may help maintain vascular stability through A2M regulation.
- NR4A receptors boost A2M, a natural enzyme blocker, in blood vessel cells
- Increased A2M reduces harmful MMP-2 and MMP-9 enzyme activity
- A2M is naturally present in human blood vessel walls
- NR4A receptors directly control A2M production via DNA binding
- This pathway may protect blood vessels from damage
Direct conversion of human fibroblasts into dopaminergic neural progenitor-like cells using TAT-mediated protein transduction of recombinant factors.
Mirakhori F, Zeynali B, Rassouli H, Salekdeh GH, Baharvand H
This study shows a method to turn human skin cells directly into dopaminergic neural progenitor cells using protein delivery and small molecules, which could lead to new cell therapies for Parkinson's disease and related conditions.
- Skin cells were converted into dopamine-producing neural progenitors
- The process uses safe protein delivery without genetic modification
- Cells expressed key markers for midbrain dopamine development
- Potential for future cell therapies in neurodegenerative diseases
Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative Stress-induced Necrosis.
Watanabe T, Sekine S, Naguro I, Sekine Y, Ichijo H
Oxidative stress triggers a specific cell death pathway where the NR4A2 protein moves from the nucleus to the cytoplasm, a process driven by the ASK1-p38 signaling pathway. This shift turns NR4A2 into a promoter of necrotic cell death, independent of apoptosis or other known necrosis pathways.
- NR4A2 moves to the cytoplasm during oxidative stress
- This movement requires p38 phosphorylation of NR4A2
- NR4A2 drives necrosis, not apoptosis
- The process does not involve caspases or RIP1/RIP3
- ASK1-p38 pathway is essential for this cell death
Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson's disease.
Esteves M, Cristóvão AC, Saraiva T, Rocha SM, Baltazar G, Ferreira L, Bernardino L
Retinoic acid delivered in nanoparticles protects dopamine-producing brain cells in a mouse model of Parkinson's disease, reducing cell loss and improving nerve connections. The treatment also boosts levels of Nurr1, a key protein involved in dopamine neuron health.
- Retinoic acid nanoparticles protect dopamine neurons
- Reduces neuron loss in Parkinson's mouse model
- Boosts Nurr1, a critical protein for dopamine cells
- May slow Parkinson's disease progression
- Represents a promising new treatment approach