High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.
Wang X, Yang C, Ihsan A, Luo X, Guo P, Cheng G, Dai M, Chen D, Liu Z, Yuan Z
N1-desoxy metabolites of certain quinoxaline antibiotics are highly toxic to adrenal cells and reduce aldosterone production by suppressing key genes and proteins involved in hormone synthesis. Natural antioxidants called OPC can protect adrenal cells by restoring the expression of these critical genes.
- N1-desoxy metabolites of quinoxaline drugs are toxic to adrenal cells
- These metabolites reduce aldosterone by lowering key enzyme genes
- Oligomeric proanthocyanidins (OPC) protect adrenal cells
- OPC restore gene expression and hormone production
- Findings may guide safer drug design and food safety rules
Parkinson's Disease, Diabetes and Cognitive Impairment.
Ashraghi MR, Pagano G, Polychronis S, Niccolini F, Politis M
This narrative review discusses shared biological mechanisms between Parkinson's disease, diabetes, and cognitive impairment, highlighting potential repurposing of anti-diabetic drugs. It mentions patents targeting Nurr1 (NR4A2) but does not provide specific clinical data or treatment outcomes for NR4A2-related syndromes.
- The paper reviews shared pathophysiology between Parkinson's, diabetes, and cognitive impairment.
- Anti-diabetic agents like GLP-1 agonists show promise in animal and human studies for Parkinson's.
- Recent patents target Nurr1, PINK1, and NrF2 proteins for novel Parkinson's treatments.
- The review does not report clinical results or genetic findings specific to NR4A2 mutations.
[Pathological mechanism of secondary-progressive multiples sclerosis and its animal model].
Oki S
This study identifies a specific immune cell type that drives the progressive neurodegeneration seen in secondary-progressive multiple sclerosis. It reveals that these cells release an enzyme that triggers inflammation, offering a potential new target for therapies aimed at slowing disease progression.
- NR4A2 is linked to early MS symptoms, not the progressive phase studied here.
- Eomes-expressing CD4+ T cells drive late-stage neurodegeneration in this model.
- Granzyme B from these cells activates receptors causing brain inflammation.
- Targeting Eomes or its enzyme may help treat progressive MS.
Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression.
Saito-Hakoda A, Uruno A, Yokoyama A, Shimizu K, Parvin R, Kudo M, Saito-Ito T, Sato I, Kogure N, Suzuki D, Shimada H, Yoshikawa T, Fujiwara I, Kagechika H, Iwasaki Y, Kure S, Ito S, Sugawara A
RXR agonists suppress tumor growth and ACTH secretion in pituitary corticotroph tumors by downregulating Nurr1 expression. This mechanism suggests potential therapeutic value for Cushing's disease but does not address NR4A2-related neurodevelopmental syndromes.
- RXR agonists induce apoptosis and inhibit proliferation in pituitary tumor cells.
- Treatment reduces ACTH secretion by suppressing Nurr1 transcription factor expression.
- The study focuses on Cushing's disease, not NR4A2-related developmental disorders.
- Findings are preclinical, using cell lines and mouse models only.
Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis.
Chen P, Li J, Huo Y, Lu J, Wan L, Li B, Gan R, Guo C
NR4A2 levels are reduced in liver cells during fibrosis, and low NR4A2 leads to increased cell growth and scarring. Restoring NR4A2 activity may help slow or stop liver damage by regulating key cell pathways.
- NR4A2 is lower in fibrotic liver tissue
- Low NR4A2 increases scar-forming cell growth
- NR4A2 helps control liver scarring via MAPK pathway
- Boosting NR4A2 could be a treatment strategy
Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.
Yazdani N, Parker CC, Shen Y, Reed ER, Guido MA, Kole LA, Kirkpatrick SL, Lim JE, Sokoloff G, Cheng R, Johnson WE, Palmer AA, Bryant CD
This study identifies Hnrnph1 as a gene that regulates sensitivity to methamphetamine in mice by influencing the expression of Nr4a2, a transcription factor critical for dopaminergic neuron development. The research demonstrates that reducing Hnrnph1 levels lowers Nr4a2 expression and decreases behavioral responses to stimulants in animal models.
- Hnrnph1 regulates methamphetamine sensitivity in mice through dopaminergic pathways.
- Reduced Hnrnph1 leads to decreased Nr4a2 expression in the striatum.
- Nr4a2 is essential for midbrain dopaminergic neuron development.
- The study uses mouse models, not human participants or clinical data.
Selective early expression of the orphan nuclear receptor Nr4a2 identifies the claustrum homolog in the avian mesopallium: Impact on sauropsidian/mammalian pallium comparisons.
Puelles L, Ayad A, Alonso A, Sandoval JE, MartÍnez-de-la-Torre M, Medina L, Ferran JL
This study identifies a brain region in chickens that corresponds to the claustrum in mammals based on early Nr4a2 gene expression. It maps the developmental timing and location of these cells to compare avian and mammalian brain structures. The research focuses entirely on evolutionary neuroanatomy rather than human disease mechanisms or treatments.
- Nr4a2 marks an early-developing brain region in chickens comparable to the mammalian claustrum.
- The study compares spatial and chronological gene expression patterns across species.
- It proposes a homologous relationship between avian mesopallium and mammalian insula/claustrum.
- The research uses chicken and turtle models for evolutionary brain mapping.
- No human data, clinical outcomes, or therapeutic implications are presented.
Coalition of Nuclear Receptors in the Nervous System.
Förthmann B, Aletta JM, Lee YW, Terranova C, Birkaya B, Stachowiak EK, Stachowiak MK, Claus P
This review describes how the nuclear form of the FGFR1 receptor interacts with other proteins, including Nurr1 (NR4A2), to regulate gene expression during neural development. It highlights specific molecular coalitions involved in neuronal stem cell differentiation and the formation of dopaminergic neurons.
- FGFR1 acts as a central signaling module directing post-mitotic neural cell development.
- The paper details FGFR1 interactions with Nurr1 during mesencephalic dopaminergic neuron development.
- It explores how nerve growth factor signaling modulates these nuclear receptor coalitions.
- The focus is on non-canonical tyrosine kinase signaling mechanisms in neurons.
Zdhhc15b Regulates Differentiation of Diencephalic Dopaminergic Neurons in zebrafish.
Wang F, Chen X, Shi W, Yao L, Gao M, Yang Y, Hao A
This study shows that the gene Zdhhc15b is essential for the development of dopamine-producing neurons in zebrafish, as reducing its function leads to fewer mature neurons and behavioral deficits. The research identifies Nurr1 (NR4A2) as a key downstream target whose expression drops when Zdhhc15b is impaired, linking this protein to dopaminergic differentiation.
- Zdhhc15b knockdown reduces mature dopamine neurons and shrinks the zebrafish diencephalon.
- Reduced Zdhhc15b lowers expression of Nurr1, FoxA2, and Lmx1a transcription factors.
- Impaired Zdhhc15b causes poor learning behavior in zebrafish models.
- Zdhhc15b regulates neuronal fate decisions rather than cell survival or proliferation.
The Key Proteins of Dopaminergic Neurotransmission of Human Peripheral Blood Lymphocytes: Changed mRNA Level in Alcohol Dependence Syndrome.
Taraskina AE, Grunina MN, Zabotina AM, Nasyrova RF, Ivanov MV, Krupitsky EM, Schwartzman AL
People with alcohol dependence show higher levels of SNCA and DRD4 genes in blood cells, but no change in NR4A2, which is the gene linked to your child's condition. These gene changes may help track the condition but are not directly related to NR4A2-related syndrome.
- SNCA and DRD4 are elevated in alcohol dependence
- NR4A2 levels unchanged in this study
- Blood gene levels may serve as markers
- Findings not relevant to NR4A2-related syndrome
- No therapeutic implications for NR4A2
Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes.
Arvind P, Jayashree S, Jambunathan S, Nair J, Kakkar VV
This study investigates gene expression changes in blood samples from adults with coronary artery disease, identifying NR4A2 as one of several genes with altered activity. It does not provide information on the role of NR4A2 in neurodevelopment or its relevance to your child's specific syndrome.
- Researchers analyzed blood gene expression in adults with coronary artery disease versus healthy controls.
- NR4A2 was among the genes validated as having different expression levels in patients.
- The study focuses on cardiovascular inflammation and immune response pathways.
- No findings relate to brain development, dopamine systems, or pediatric neurology.
low2015-11-26 · Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology
Structure of distress call: implication for specificity and activation of dopaminergic system.
Mariappan S, Bogdanowicz W, Raghuram H, Marimuthu G, Rajan KE
Distress calls in fruit bats contain specific information about stress that triggers a dopamine-related brain response in both callers and listeners, suggesting the call structure directly activates the brain's stress and social communication pathways.
- Distress calls signal stress and attract other bats
- Natural calls activate dopamine brain circuits more than altered calls
- Brain changes occur in areas linked to emotion and social response
- Call structure is critical for triggering the correct neural response
Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression.
Bordoni L, Nasuti C, Mirto M, Caradonna F, Gabbianelli R
Early-life exposure to the pesticide permethrin causes lasting changes in DNA methylation and Nurr1 gene expression that pass from exposed parents to their untreated offspring. This intergenerational damage suggests that environmental toxins can alter genetic regulation in ways that affect future generations.
- Permethrin exposure in early life alters Nurr1 gene expression in rat offspring.
- Mothers and offspring show decreased global DNA methylation after exposure.
- One-third of progeny exhibit the same Nurr1 alterations as exposed parents.
- This is the first identified case of intergenerational pesticide-induced damage.
Optogenetic Inhibitor of the Transcription Factor CREB.
Ali AM, Reis JM, Xia Y, Rashid AJ, Mercaldo V, Walters BJ, Brechun KE, Borisenko V, Josselyn SA, Karanicolas J, Woolley GA
Researchers develop a light-controlled tool to inhibit the transcription factor CREB, which successfully regulates NR4A2 expression in neurons. This method allows precise spatiotemporal control of gene activity using blue light.
- The tool opto-DN-CREB inhibits CREB function when exposed to blue light.
- It works by preventing CREB from binding to its target DNA sites.
- Blue light activation controls NR4A2 and c-Fos expression in neurons.
- This approach offers a general method for controlling native transcriptional events.
Development and function of the midbrain dopamine system: what we know and what we need to.
Bissonette GB, Roesch MR
This review summarizes current knowledge on how midbrain dopamine neurons develop and function, linking these processes to movement disorders like Parkinson's disease as well as conditions such as autism and schizophrenia. It highlights key molecular players involved in this development and identifies gaps in understanding that may guide future research into dopamine-related disorders.
- Midbrain dopamine neuron development is linked to Parkinson's, autism, and schizophrenia.
- Review covers major molecular and genetic factors in dopamine neuron ontogeny.
- Identifies knowledge gaps for future study on dopamine-related disorders.
- Aims to bridge developmental and behavioral neuroscience fields.
Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.
Wei X, Gao H, Zou J, Liu X, Chen D, Liao J, Xu Y, Ma L, Tang B, Zhang Z, Cai X, Jin K, Xia Y, Wang Q
This study shows that memantine protects dopaminergic neurons in a cell culture model of Parkinson's disease by balancing the opposing actions of two related proteins, Nur77 and Nurr1. Memantine reduces harmful mitochondrial stress caused by Nur77 while restoring protective signals from Nurr1.
- Memantine restores balance between Nur77 and Nurr1 in damaged dopaminergic cells.
- Nur77 promotes cell death via mitochondrial impairment, while Nurr1 supports survival.
- The drug reduces harmful protein movement within the cell under stress conditions.
- Knocking down Nur77 mimics some protective effects of memantine in these cells.
Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.
Volakakis N, Tiklova K, Decressac M, Papathanou M, Mattsson B, Gillberg L, Nobre A, Björklund A, Perlmann T
This study shows that Nurr1 protects dopamine neurons by regulating the Ret signaling pathway, which is disrupted by alpha-synuclein toxicity. While the specific drug tested (bexarotene) failed to protect neurons in live rats, it successfully restored this protective signaling in laboratory cells.
- Nurr1 restores hundreds of genes disrupted by alpha-synuclein in dopamine neurons.
- Bexarotene activates Nurr1 partners to restore Ret neurotrophic signaling in cells.
- Bexarotene failed to provide neuroprotection in a live rat Parkinson's model.
- The study highlights the Nurr1-Ret pathway as a potential therapeutic target.
Modulation by Trace Amine-Associated Receptor 1 of Experimental Parkinsonism, L-DOPA Responsivity, and Glutamatergic Neurotransmission.
Alvarsson A, Zhang X, Stan TL, Schintu N, Kadkhodaei B, Millan MJ, Perlmann T, Svenningsson P
This study investigates how the TAAR1 receptor influences dopamine and glutamate signaling in mouse models of Parkinson's disease. It finds that blocking TAAR1 reduces dopaminergic neuron loss but worsens L-DOPA side effects, while activating TAAR1 protects neurons and reduces dyskinesia.
- TAAR1 activation protects dopaminergic neurons from degeneration in mouse models.
- Blocking TAAR1 increases L-DOPA-induced dyskinesia and rotational behavior in mice.
- TAAR1 modulates glutamate neurotransmission similarly to dopamine D2 receptors.
- The research focuses on molecular mechanisms, not human clinical outcomes.
Dissecting the role of Engrailed in adult dopaminergic neurons--Insights into Parkinson disease pathogenesis.
Rekaik H, Blaudin de Thé FX, Prochiantz A, Fuchs J, Joshi RL
This review explains how the Engrailed proteins support adult dopamine neuron survival and mitochondrial function, offering mechanistic context for why dopaminergic pathways are vulnerable in neurodevelopmental disorders. It highlights that multiple transcription factors, including Nurr1 (NR4A2), work together to maintain these neurons throughout life.
- Engrailed proteins protect adult dopamine neurons by regulating mitochondrial energy production.
- Loss of Engrailed causes progressive dopamine neuron death and Parkinson-like symptoms in mice.
- Nurr1 (NR4A2) works alongside other factors to maintain adult dopamine neuron survival.
- The paper reviews molecular mechanisms rather than testing treatments or human outcomes.
Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation.
Raveney BJ, Oki S, Hohjoh H, Nakamura M, Sato W, Murata M, Yamamura T
This study identifies a specific type of immune cell, Eomes-expressing T-helper cells, as the primary driver of chronic neuroinflammation in mouse models and progressive multiple sclerosis patients. It demonstrates that removing these cells reduces disease severity, highlighting a potential new target for treating inflammatory neurological conditions.
- Eomes-expressing CD4+ T cells drive late-onset neuroinflammation in mice.
- Deleting the Eomes gene significantly improves symptoms in chronic disease models.
- These specific immune cells are elevated in progressive multiple sclerosis patients.
- The mechanism involves granzyme B and protease-activated receptor-1 pathways.
Differentiation of stem cells derived from carious teeth into dopaminergic-like cells.
Gnanasegaran N, Govindasamy V, Abu Kasim NH
Stem cells from decayed teeth can turn into dopamine-producing cells, but they do so less efficiently than stem cells from healthy teeth, suggesting they may not be ideal for treating conditions like NR4A2-related syndrome.
- Stem cells from decayed teeth make fewer dopamine-like cells
- Key brain cell genes like NURR1 are less active in these cells
- Cells from healthy teeth work better for dopamine cell production
- Not all stem cell sources are equal for brain repair therapies
- More testing is needed before using these cells in treatment
Parathyroid hormone 1 receptor is essential to induce FGF23 production and maintain systemic mineral ion homeostasis.
Fan Y, Bi R, Densmore MJ, Sato T, Kobayashi T, Yuan Q, Zhou X, Erben RG, Lanske B
This study shows that the PTH1 receptor in bones is essential for producing FGF23, a key hormone that controls phosphate and vitamin D levels in the blood. Without this receptor, the body cannot properly regulate mineral balance, leading to low phosphate, low vitamin D, and excessive loss of calcium and phosphate in urine.
- PTH1R in bones triggers FGF23 production
- Loss of PTH1R reduces FGF23 by half
- Mineral balance is disrupted without PTH1R signaling
- Kidney genes that manage minerals are suppressed
- PTH cannot boost FGF23 or Nurr1 without PTH1R
Noggin Over-Expressing Mouse Embryonic Fibroblasts and MS5 Stromal Cells Enhance Directed Differentiation of Dopaminergic Neurons from Human Embryonic Stem Cells.
Lim MS, Shin MS, Lee SY, Minn YK, Hoh JK, Cho YH, Kim DW, Lee SH, Kim CH, Park CH
Adding noggin to the culture system improves the efficiency of converting human embryonic stem cells into dopaminergic neurons. This method increases the expression of key midbrain dopamine markers and reduces undifferentiated cell populations.
- Noggin exposure enhances directed differentiation of human embryonic stem cells into dopaminergic precursors.
- The approach boosts expression of midbrain-specific markers like En-1, Lmx1b, and Nurr1.
- Tyrosine hydroxylase levels increase, indicating successful maturation toward dopamine-producing neurons.
- Undifferentiated marker Oct3/4 decreases as cells commit to the dopaminergic lineage.
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 uses computational methods to predict how genetic variations in immune system genes affect disease susceptibility for tuberculosis and HIV/AIDS. It identifies NR4A2 as one of several transcription factors that may bind to these gene regions, but it does not investigate NR4A2's role in brain development or neurological function.
- The research focuses on antimicrobial genes DEFB1 and CAMP, not NR4A2 or neurological pathways.
- NR4A2 appears only as one of many transcription factors analyzed for immune disease binding.
- The study develops a computational algorithm for predicting regulatory SNPs in immune contexts.
- No clinical data, patient phenotypes, or dopaminergic mechanisms are examined.
Nurr1 reduction influences the onset of chronic EAE in mice.
Montarolo F, Perga S, Martire S, Bertolotto A
Reducing Nurr1 levels in mice accelerates the onset of an inflammatory disease model and increases spinal cord inflammation. This finding highlights a role for Nurr1 in regulating early immune responses within the central nervous system. The study does not provide evidence on human symptoms, treatment efficacy, or genetic variants relevant to NR4A2 syndrome.
- Nurr1 reduction accelerates disease onset in an inflammatory mouse model.
- Lower Nurr1 levels increase inflammatory cell infiltration in the spinal cord.
- The study uses heterozygous knockout mice, not human patients.
- Results focus on general neuroinflammation mechanisms rather than NR4A2-specific phenotypes.
- No clinical data or treatment implications for humans are presented.
Animal models of Parkinson's disease: An updated overview.
Gubellini P, Kachidian P
This review summarizes various animal models used to study Parkinson's disease, including those that disrupt the Nurr1 gene. It does not provide new clinical data or treatment outcomes for children with NR4A2-related syndromes.
- The paper reviews classic and genetic animal models of Parkinson's disease.
- It discusses how these models help understand disease mechanisms and test therapies.
- Nurr1 disruption is mentioned as one method to create specific PD models in animals.
- No human patient data or direct relevance to NR4A2 syndrome treatment is included.
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 improves the differentiation of fat-derived stem cells into neuron-like cells that produce dopamine. This approach increases neuronal markers and neurite growth in a laboratory setting, suggesting potential for future cell-based therapies for neurodegenerative conditions.
- Electrical stimulation combined with Nurr-1 gene transduction enhances stem cell differentiation.
- The treated cells secrete dopamine and express key neuronal markers like MAP-2.
- This is a preclinical study using adipose tissue-derived stem cells in vitro.
- No human trials or clinical data are included in this research.
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 reduces dopamine levels and alters key gene expression in the brain regions controlling movement in male rats. This study suggests that environmental toxins can disrupt dopaminergic development, which is relevant to understanding non-genetic factors in parkinsonian symptoms.
- Atrazine exposure lowers dopamine and levodopa levels in rat brains.
- The herbicide reduces expression of Nurr1 and related developmental genes.
- Damage occurs during the pubertal period, a vulnerable developmental window.
- Findings link environmental toxins to dopaminergic system disruption.
MicroRNA-132 promotes estradiol synthesis in ovarian granulosa cells via translational repression of Nurr1.
Wu S, Sun H, Zhang Q, Jiang Y, Fang T, Cui I, Yan G, Hu Y
MicroRNA-132 boosts estrogen production in ovarian cells by turning down Nurr1, a protein that normally suppresses estrogen-making genes. This finding reveals a new regulatory pathway in hormone synthesis, though it is specific to ovarian function and not directly related to NR4A2/NURR1 in the brain or neurodevelopment.
- miR-132 increases estrogen by blocking Nurr1
- Nurr1 normally suppresses estrogen-making genes
- This mechanism is in ovarian cells, not brain or neurons
- No direct link to NR4A2-related neurodevelopmental disorders
- Findings are specific to hormone regulation in ovaries
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
Researchers developed a protocol to create antibodies that specifically target the Nurr1 protein without reacting with its close relatives, Nur77 and Nor1. This method involves immunizing animals with the unique parts of Nurr1 and then removing any antibodies that bind to the other similar proteins.
- The study creates specific tools for lab research on Nurr1 protein function.
- It does not test treatments or analyze patients with NR4A2 syndromes.
- The work focuses on molecular biology techniques rather than clinical outcomes.
Limitations of In Vivo Reprogramming to Dopaminergic Neurons via a Tricistronic Strategy.
Theodorou M, Rauser B, Zhang J, Prakash N, Wurst W, Schick JA
This study tested a gene therapy approach to turn brain cells into dopamine-producing neurons in mice, but the method caused cell death due to stress and poor protein processing, preventing successful reprogramming. The results highlight major biological hurdles that must be overcome before this strategy could be used to treat Parkinson’s or NR4A2-related conditions.
- A gene combo failed to reprogram brain cells in live mice
- The therapy caused cell death from stress and poor protein cleavage
- Current design cannot safely deliver the needed genes
- Better strategies are needed for in vivo reprogramming
- This approach is not ready for human use
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
This study finds that lower levels of the NR4A2 protein (Nurr1) in white blood cells correlate with higher inflammation and insulin resistance in adults with type 2 diabetes. High glucose and fat levels reduce Nurr1 expression in these cells, suggesting a link between metabolic stress and inflammatory pathways.
- NR4A2 levels drop in white blood cells when exposed to high glucose or fats.
- Low NR4A2 correlates with higher inflammation markers TNFα and IL-6.
- This association links reduced NR4A2 to insulin resistance in type 2 diabetes.
- The study uses human patient samples but focuses on metabolic disease mechanisms.
FGF23 gene regulation by 1,25-dihydroxyvitamin D: opposing effects in adipocytes and osteocytes.
Kaneko I, Saini RK, Griffin KP, Whitfield GK, Haussler MR, Jurutka PW
The FGF23 gene is turned on by vitamin D in bone cells but turned off in fat cells, due to a specific DNA switch that responds differently depending on the cell type. This switch involves a key protein called Nurr1, which may help explain how vitamin D and calcium regulate FGF23 in the body.
- Vitamin D increases FGF23 in bone cells but decreases it in fat cells
- A DNA region near the FGF23 gene acts as a switch using Nurr1 and vitamin D receptors
- This switch may explain why FGF23 responds differently in various tissues
- Calcium also boosts FGF23 production in bone cells
- The findings reveal how FGF23 is regulated in health and disease
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
Researchers developed a new sensor to measure how specific drugs interact with Nur77/RXR and Nurr1/RXR protein complexes. They found that the drug SR11237 selectively activates the Nur77/RXR complex more than other combinations. This tool helps identify compounds that target specific nuclear receptor pairs.
- New BRET sensor measures coactivator recruitment by specific NR dimers.
- SR11237 shows stronger activity on Nur77/RXR than Nurr1/RXR.
- Rexinoids often lack selectivity for specific heterodimer complexes.
- Technology aids in finding compounds with dimer-specific specificity.
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
This study shows that adenosine regulates NR4A2 to suppress inflammation in immune cells, but it does not address the neurological or developmental aspects of NR4A2-related syndrome. The findings are limited to monocytes and macrophages, with no connection to dopaminergic neurons or human clinical outcomes for this specific genetic condition. Consequently, this research offers no direct insight into treatment or management for a child with an NR4A2 variant.
- Adenosine activates NR4A2 in immune cells to reduce inflammatory cytokine production.
- NR4A2 depletion increases NF-κB activity and hyperinflammation in monocytes.
- The study focuses on innate immunity, not the nervous system.
- No human clinical data or dopaminergic neuron mechanisms are presented.
- Findings do not translate to NR4A2-related syndrome pathophysiology.