Reduced tyrosine hydroxylase and GTP cyclohydrolase mRNA expression, tyrosine hydroxylase activity, and associated neurochemical alterations in Nurr1-null heterozygous mice.
Eells JB, Misler JA, Nikodem VM
Reduced Nurr1 levels in mice lead to lower dopamine production due to decreased activity of key enzymes involved in dopamine synthesis, especially in brain regions linked to reward and motivation. This affects dopamine levels differently in various brain circuits, with more severe impacts in areas like the nucleus accumbens.
- Nurr1 deficiency reduces dopamine-making enzymes
- Dopamine synthesis is impaired in key brain areas
- Nucleus accumbens shows consistent dopamine deficits
- Enzyme changes affect dopamine levels under stress
- Nurr1 helps control dopamine production machinery
Stable expression of a neuronal dopaminergic progenitor phenotype in cell lines derived from human amniotic fluid cells.
McLaughlin D, Tsirimonaki E, Vallianatos G, Sakellaridis N, Chatzistamatiou T, Stavropoulos-Gioka C, Tsezou A, Messinis I, Mangoura D
Amniotic fluid cells can be grown into stable cell lines that behave like early dopaminergic neurons, expressing key proteins needed for dopamine production and nerve function. These cells maintain their specialized identity over many generations and resemble neurons found in the midbrain.
- Amniotic fluid cells form stable cell lines with dopaminergic traits
- Cells express NURR1 and other markers critical for dopamine neurons
- The cell lines maintain their neuron-like properties for over 30 passages
- They mimic early midbrain dopaminergic neurons seen in development
- Potential for studying NR4A2/NURR1-related disorders and therapies
Early postnatal isolation reduces dopamine levels, elevates dopamine turnover and specifically disrupts prepulse inhibition in Nurr1-null heterozygous mice.
Eells JB, Misler JA, Nikodem VM
Mice with one defective copy of the NR4A2 gene (Nurr1) show worsened brain function and behavior when raised in isolation after weaning, especially in how they process sensory information. This suggests that environmental stress like isolation can trigger symptoms in genetically vulnerable individuals, mirroring aspects of human neuropsychiatric disorders.
- Isolation after weaning worsens sensory processing in NR4A2-deficient mice
- Genetic vulnerability plus environmental stress disrupts dopamine function
- This model mimics gene-environment interactions seen in human mental health conditions
- Dopamine levels and brain chemistry are altered by both genetics and isolation
- Findings may help explain why some children with NR4A2 mutations develop symptoms
Reduction of dopamine-related transcription factors Nurr1 and NGFI-B in the prefrontal cortex in schizophrenia and bipolar disorders.
Xing G, Zhang L, Russell S, Post R
People with schizophrenia and bipolar disorder have lower levels of two key brain proteins, Nurr1 and NGFI-B, in the prefrontal cortex, which may contribute to dopamine-related brain dysfunction seen in these conditions.
- Nurr1 and NGFI-B are critical for dopamine brain function
- Levels of both proteins are reduced in schizophrenia and bipolar disorder
- Lower levels found in brain regions linked to thinking and behavior
- This may explain some dopamine-related symptoms in these disorders
- Could point to new treatment targets in the future
The dopamine D2 receptor regulates the development of dopaminergic neurons via extracellular signal-regulated kinase and Nurr1 activation.
Kim SY, Choi KC, Chang MS, Kim MH, Kim SY, Na YS, Lee JE, Jin BK, Lee BH, Baik JH
Dopamine D2 receptors help guide the development of dopamine-producing brain cells by activating a key protein called Nurr1 through a signaling pathway involving ERK. This process is essential for forming proper dopamine circuits, and its disruption may contribute to neurodevelopmental disorders.
- D2 receptors help build dopamine neurons via Nurr1 activation
- Nurr1 and ERK signaling are critical for dopamine neuron development
- Without D2 receptors, fewer dopamine neurons form
- Activating D2 receptors boosts neuron growth and connections
- This pathway may be a target for treating NR4A2-related disorders
Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia.
Schmidt-Kastner R, van Os J, W M Steinbusch H, Schmitz C
Many genes linked to schizophrenia are influenced by low oxygen levels during brain development, and some are also involved in blood vessel function. This suggests that oxygen deprivation in the fetal brain may disrupt the activity of these genes, potentially contributing to neurodevelopmental issues seen in schizophrenia. The NR4A2/NURR1 gene is among those affected by hypoxia and may play a role in this process.
- Over half of schizophrenia-linked genes are affected by low oxygen during development
- NR4A2/NURR1 is regulated by hypoxia and may be disrupted in fetal brain development
- Hypoxia may alter gene activity linked to schizophrenia risk
- Some of these genes are also involved in blood vessel function in the brain
- Future research should consider oxygen levels and blood flow in neurodevelopment
Neuropilin1 is a direct downstream target of Nurr1 in the developing brain stem.
Hermanson E, Borgius L, Bergsland M, Joodmardi E, Perlmann T
Nurr1 directly controls the expression of Neuropilin-1 (Nrp1), a gene involved in axon guidance and blood vessel formation, in the brain stem. This finding suggests Nurr1 may influence neural circuit development and respiratory function through Nrp1 regulation.
- Nurr1 directly activates the Nrp1 gene
- Nrp1 is coexpressed with Nurr1 in the brain stem
- Nrp1 levels drop in Nurr1-deficient mice
- Nurr1 binds to the Nrp1 gene promoter
- This links Nurr1 to axon guidance and brain stem development
Induction dopamine releasing cells from mouse embryonic stem cells and their long-term culture.
Moriyasu K, Yamazoe H, Iwata H
This study shows that mouse embryonic stem cells can be turned into dopamine-releasing neurons and kept alive and functional for over two months, even when enclosed in protective gel capsules. The neurons maintained their ability to release dopamine over time, which is important for potential treatments of Parkinson's disease.
- Dopamine-releasing neurons made from mouse stem cells stay functional for 58 days
- Encapsulation in gel preserves neuron survival and function
- Neurons release dopamine consistently over time
- Gel capsules may help protect cells after transplantation
12-O-tetradecanoyl-phorbol-13-acetate-dependent up-regulation of dopaminergic gene expression requires Ras and neurofibromin in human IMR-32 neuroblastoma.
Mangoura D, Theofilopoulos S, Karouzaki S, Tsirimonaki E
In human nerve cells, a key protein called Ras and a regulator called neurofibromin control the production of dopamine by turning on the gene for tyrosine hydroxylase, which is essential for dopamine creation. This process happens through a pathway involving PKC and does not require the Nurr1 protein, suggesting alternative ways to boost dopamine production.
- Ras and neurofibromin regulate dopamine-making genes
- This happens without needing the Nurr1 protein
- Boosting Ras increases dopamine-related gene activity
- Neurofibromin's GRD domain controls Ras activity
- These findings may help develop treatments for dopamine disorders
Tyrosine hydroxylase gene regulation in human neuronal progenitor cells does not depend on Nurr1 as in the murine and rat systems.
Jin H, Romano G, Marshall C, Donaldson AE, Suon S, Iacovitti L
In human brain cells, the gene that makes dopamine (TH) is not controlled by the Nurr1 protein, unlike in mice and rats. This means treatments targeting Nurr1 may not work the same way in people with NR4A2-related syndrome as they do in animal models.
- Human TH gene regulation does not need Nurr1
- Nurr1 does not bind to human TH promoter
- TH gene activity in humans is independent of Nurr1
- Animal model findings do not apply to humans
- Therapies targeting Nurr1 may not help human patients
Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitro.
Chung S, Shin BS, Hwang M, Lardaro T, Kang UJ, Isacson O, Kim KS
Embryonic stem cell-derived neural precursors can be expanded in the lab while still retaining their ability to become dopamine-producing neurons, unlike those from fetal brain tissue, which lose this potential during expansion. This suggests a more reliable source for cell therapies targeting dopamine-related disorders.
- ES cell-derived neural precursors keep dopamine neuron potential after expansion
- Fetal brain-derived precursors lose this ability during lab growth
- ES-derived neurons produce key dopamine markers and release dopamine
- These cells can be frozen and remain functional
- Transplanted ES-derived cells form dopamine neurons in mice
Adult rat bone marrow stromal cells express genes associated with dopamine neurons.
Kramer BC, Woodbury D, Black IB
Adult rat bone marrow stromal cells naturally express key genes needed for dopamine neuron development and survival, including Nurr-1, and respond to signaling pathways like Shh and GDNF, suggesting they could be used to treat Parkinson’s disease.
- MSCs express Nurr-1, critical for dopamine neuron development
- They produce multiple genes linked to dopamine neuron survival and function
- MSCs respond to Shh and GDNF—key growth signals for dopamine neurons
- These cells may serve as a cell therapy source for Parkinson’s disease
Influence of retinoic acid and lithium on proliferation and dopaminergic potential of human NT2 cells.
Misiuta IE, Saporta S, Sanberg PR, Zigova T, Willing AE
The study used human NT2 cells, a model for neural progenitor cells, to test how retinoic acid and lithium affect cell growth and the development of dopamine-producing neurons. Lithium boosted cell survival and growth but did not increase key genes needed for dopamine neuron development. The NT2 cell line remains a useful tool for testing drugs that affect neural cell behavior.
- Lithium increases NT2 cell survival and growth
- Lithium did not boost dopamine neuron genes
- NT2 cells are a good model for testing neural drugs
- Retinoic acid did not activate key dopamine genes
- No change in dopamine neuron development with lithium
The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory disease.
O'Kane M, Murphy EP, Kirby B
Corticotropin-releasing hormone (CRH) and its receptor NURR1 are active in the skin and may drive inflammation in stress-related skin diseases like psoriasis. CRH can activate immune cells and influence pathways linked to inflammatory skin conditions, suggesting a potential role in disease development and treatment.
- CRH and NURR1 are found in the skin and may drive inflammation
- Stress can activate CRH, worsening skin inflammation
- NURR1 is linked to immune regulation and psoriasis
- CRH may connect brain stress responses to skin disease
- Targeting CRH or NURR1 could be a future treatment strategy
Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype.
Martinat C, Bacci JJ, Leete T, Kim J, Vanti WB, Newman AH, Cha JH, Gether U, Wang H, Abeliovich A
Nurr1 and Pitx3 work together to guide stem cells to become mature midbrain dopamine neurons, which are the cells lost in Parkinson's disease. This cooperation is key to producing functional neurons in lab cultures, offering insights for future cell-based therapies.
- Nurr1 and Pitx3 must work together to create mature dopamine neurons
- This process is essential for generating cells used in potential Parkinson's treatments
- The findings apply to both mouse and human stem cells
- The cooperation drives terminal maturation of stem cells into midbrain neurons
Identification of novel genes regulated in the developing human ventral mesencephalon.
Jørgensen JR, Juliusson B, Henriksen KF, Hansen C, Knudsen S, Petersen TN, Blom N, Seiger A, Wahlberg LU
This study identifies genes active in the developing human brain region that produces dopamine neurons, including a key gene called NURR1. It found several new genes that are turned on or off in the right place and time to help form these neurons, which may help develop treatments for Parkinson's disease.
- Identified genes active in human dopamine neuron development
- Confirmed NURR1's role in early brain development
- Discovered new genes linked to dopamine neuron formation
- Found potential targets for regenerative therapies
- Used real human embryonic tissue for accuracy
Gene induction during differentiation of human pulmonary type II cells in vitro.
Wade KC, Guttentag SH, Gonzales LW, Maschhoff KL, Gonzales J, Kolla V, Singhal S, Ballard PL
This study identifies genes that turn on during the development of human lung type II cells, which produce surfactant needed for breathing after birth. It highlights NR4A2 as one of several key regulatory genes strongly activated during this process, along with known surfactant genes and others involved in metabolism and cell structure.
- NR4A2 is strongly induced during human lung type II cell development
- NR4A2 is part of a group of genes linked to surfactant production and cell function
- The study confirms gene activation at both mRNA and protein levels
- Findings may help understand lung development and surfactant disorders
- Lysosomal protein LAMP3, linked to NR4A2, localizes to surfactant storage sites
The NR4A subgroup: immediate early response genes with pleiotropic physiological roles.
Maxwell MA, Muscat GE
NR4A2 (Nurr1) is a key gene involved in brain development and function, and mutations in this gene cause a rare neurodevelopmental disorder. The protein it produces helps regulate gene activity in response to cellular stress and signals, and its dysfunction is linked to neurological symptoms seen in affected children.
- NR4A2 is essential for brain development and function
- Mutations cause a rare neurodevelopmental syndrome
- The protein responds to stress and environmental signals
- It regulates gene activity without needing a hormone
- Dysfunction leads to neurological and developmental issues
Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation.
Wingate AD, Campbell DG, Peggie M, Arthur JS
Nur77, a protein linked to brain development and function, is modified by RSK kinase in response to cell growth signals, which may affect its role in gene regulation and cell survival. This modification also occurs in two related proteins, Nurr1 and Nor1, suggesting a shared regulatory mechanism.
- Nur77 is phosphorylated by RSK in response to growth signals
- This modification may influence Nur77's ability to regulate genes
- The same process affects Nurr1 and Nor1, related brain proteins
- RSK is activated by the MAPK pathway, a key cellular signaling route
Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons.
Kele J, Simplicio N, Ferri AL, Mira H, Guillemot F, Arenas E, Ang SL
Neurogenin 2 (Ngn2) is essential for turning early brain stem cells into dopamine-producing neurons in the midbrain, and without it, these critical neurons fail to develop properly.
- Ngn2 is required to make dopamine neurons from brain stem cells
- Without Ngn2, dopamine neuron development stops early
- Mash1 can partly replace Ngn2, but only weakly
- Ngn2 acts at a key step in turning stem cells into dopamine neurons
- This process happens in the ventral midbrain, where dopamine neurons form
Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon.
Thompson LH, Andersson E, Jensen JB, Barraud P, Guillemot F, Parmar M, Björklund A
Cells expressing the Ngn2 gene in the developing brain can become dopamine neurons and survive after transplantation, making them promising for treating conditions like NR4A2-related syndrome. These Ngn2-expressing cells are the only ones that become dopamine neurons, and they can be isolated and used in transplants.
- Ngn2 marks dopamine neuron precursors in the brain
- These cells can become mature dopamine neurons after transplant
- Ngn2 cells are the only source of dopamine neurons in this region
- The Ngn2-GFP tool helps isolate transplantable dopamine precursors
- This could lead to better cell therapies for dopamine-related disorders
Nurr1 in Parkinson's disease and related disorders.
Chu Y, Le W, Kompoliti K, Jankovic J, Mufson EJ, Kordower JH
Nurr1 levels are significantly reduced in dopamine-producing neurons in Parkinson's disease, especially in cells with abnormal protein clumps, and this decline is linked to the loss of dopamine-making enzymes. The same pattern occurs in Alzheimer's and progressive supranuclear palsy, suggesting Nurr1 deficiency is tied to neurodegeneration across multiple brain disorders.
- Nurr1 is low in dopamine neurons in Parkinson's disease
- Low Nurr1 matches loss of dopamine-making enzymes
- Nurr1 decline seen in Alzheimer's and PSP too
- Nurr1 loss correlates with brain cell damage
- Nurr1 may be a key player in multiple neurodegenerative diseases
[Recent advances in Nurr1 gene differentiating stem cells into dopaminergic neuron].
Gao FY, Yang H, Zhang ZY
Research shows that the NR4A2 gene, also known as Nurr1, plays a critical role in turning stem cells into dopamine-producing neurons, which are essential for brain function and are lost in conditions like Parkinson’s disease.
- NR4A2/Nurr1 directs stem cells to become dopamine neurons
- This process is vital for brain development and repair
- Understanding NR4A2 helps in developing cell-based therapies
- May inform treatments for NR4A2-related neurodevelopmental disorders
One-step induction of neurons from mouse embryonic stem cells in serum-free media containing vitamin B12 and heparin.
Yamazoe H, Kobori M, Murakami Y, Yano K, Satoh M, Mizuseki K, Sasai Y, Iwata H
This study developed a simple method to turn mouse embryonic stem cells into dopamine-producing neurons using serum-free media with vitamin B12 and heparin, without needing expensive growth factors or forming embryoid bodies. The resulting neurons expressed key markers of midbrain dopaminergic cells and released dopamine, suggesting potential for cell therapy in Parkinson’s disease.
- Vitamin B12 and heparin alone induce dopamine neurons from mouse stem cells
- No expensive cytokines or embryoid bodies needed
- Neurons release dopamine and express key dopaminergic markers
- Combining with putrescine, biotin, and Fe2+ boosts neuron yield and dopamine output
- Method could help develop cell therapies for Parkinson’s disease
The role of Pitx3 in survival of midbrain dopaminergic neurons.
Smits SM, Smidt MP
Pitx3 is a key transcription factor that helps midbrain dopaminergic neurons develop and survive, and it works alongside other genes like Nurr1 and Lmx1b to guide the formation of these critical brain cells.
- Pitx3 is essential for the survival of dopamine-producing neurons
- It helps control how these neurons form and mature in the brain
- Pitx3 works with other genes like Nurr1 and Lmx1b
- Understanding Pitx3 may help develop stem cell therapies for Parkinson’s
- This research informs how dopamine neurons develop in humans
Knockdown of Nurr1 in the rat hippocampus: implications to spatial discrimination learning and memory.
Colón-Cesario WI, Martínez-Montemayor MM, Morales S, Félix J, Cruz J, Adorno M, Pereira L, Colón N, Maldonado-Vlaar CS, Peña de Ortiz S
Reducing Nurr1 levels in the rat hippocampus impairs learning and memory, especially the ability to update or change learned behaviors. Rats with lower Nurr1 struggled to adapt after learning a task, showing persistent reliance on old patterns even when they were no longer correct.
- Nurr1 is needed for flexible learning and memory in the hippocampus
- Lower Nurr1 levels cause trouble updating learned behaviors
- Impaired ability to abandon outdated spatial preferences
- Nurr1 loss affects long-term memory and behavioral adaptation
Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77.
Pei L, Castrillo A, Tontonoz P
NR4A2 (Nurr1) and related proteins act as proinflammatory regulators in immune cells, boosting the expression of genes involved in inflammation and immune response, which may worsen inflammatory conditions.
- NR4A2 promotes inflammation in immune cells
- NR4A2 activates genes linked to immune response and cell signaling
- NR4A2 enhances NF-kappaB pathway activity
- This suggests NR4A2 may worsen inflammatory processes
Human fibroblast-derived cell lines have characteristics of embryonic stem cells and cells of neuro-ectodermal origin.
Rieske P, Krynska B, Azizi SA
Human fibroblasts from a lung cell line can behave like stem cells and turn into nerve-like cells, including those that make dopamine, which is relevant to NR4A2-related disorders.
- Fibroblasts can express stem cell and nerve cell genes
- They can be turned into dopamine-producing cells
- This suggests a potential path for cell-based therapies
- The process involves turning off growth genes and activating nerve genes
Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity.
Michelhaugh SK, Vaitkevicius H, Wang J, Bouhamdan M, Krieg AR, Walker JL, Mendiratta V, Bannon MJ
Multiple versions of the NURR1 protein are made in dopamine neurons, and most of these versions do not work as well as the full-length protein, which may affect how well these neurons function. Some versions even block the normal activity of NURR1, potentially contributing to the symptoms seen in NR4A2-related syndrome.
- Many NURR1 protein variants exist in dopamine neurons
- Most variants have weaker or no activity compared to full-length NURR1
- Some variants act as 'blockers' of normal NURR1 function
- This may explain why NURR1 doesn't work properly in NR4A2-related syndrome
- These variants could be targets for future treatments
Nurr1 dependent regulation of pro-inflammatory mediators in immortalised synovial fibroblasts.
Davies MR, Harding CJ, Raines S, Tolley K, Parker AE, Downey-Jones M, Needham MR
Nurr1 increases the production of inflammatory molecules like IL-8 in joint cells, suggesting it may drive inflammation in diseases like rheumatoid arthritis. This finding highlights a potential new target for reducing inflammation, though it is not directly about NR4A2-related syndrome in children.
- Nurr1 boosts IL-8, a key inflammatory signal
- Nurr1 increases other inflammatory genes in joint cells
- This may contribute to rheumatoid arthritis inflammation
- Nurr1 acts as a switch for inflammatory pathways
- Findings suggest possible anti-inflammatory treatments
Selective allosteric ligand activation of the retinoid X receptor heterodimers of NGFI-B and Nurr1.
Morita K, Kawana K, Sodeyama M, Shimomura I, Kagechika H, Makishima M
A compound called HX600 selectively activates the NGFI-B and Nurr1 proteins when they team up with RXR, a related receptor, which may help treat conditions linked to these proteins, including NR4A2-related syndromes.
- HX600 activates NGFI-B and Nurr1 when bound to RXR
- This activation happens through an allosteric mechanism
- The effect is specific to certain ligands, not natural retinoic acid
- HX600 could be a tool to study and potentially treat NR4A2-related disorders
- Findings suggest a path for targeted therapy development
The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease.
Jankovic J, Chen S, Le WD
Nurr1 is a key protein for the development and function of dopamine-producing brain cells, and its reduced activity is linked to Parkinson's disease. Low Nurr1 levels are found in the brains and blood of people with Parkinson's, and genetic changes in Nurr1 are associated with the disease.
- Nurr1 is essential for dopamine neuron development
- Nurr1 regulates dopamine production and storage
- Low Nurr1 levels are seen in Parkinson's brains and blood
- Nurr1 gene changes are linked to Parkinson's disease
- Nurr1 deficiency increases vulnerability of dopamine neurons
Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion.
Castelo-Branco G, Sousa KM, Bryja V, Pinto L, Wagner J, Arenas E
Ventral midbrain glia help develop dopamine-producing neurons by releasing a signal called Wnt-5a, which is essential for turning precursor cells into dopamine neurons. This process depends on specific genes expressed in these glial cells and may offer new ways to support brain development in NR4A2-related disorders.
- Ventral midbrain glia release Wnt-5a to help make dopamine neurons
- Wnt-5a is critical for turning precursor cells into dopamine-producing cells
- Glial cells in this region express key brain development genes
- Blocking Wnt-5a reduces dopamine neuron formation
- This mechanism may inform therapies for NR4A2-related conditions
NTera2: a model system to study dopaminergic differentiation of human embryonic stem cells.
Schwartz CM, Spivak CE, Baker SC, McDaniel TK, Loring JF, Nguyen C, Chrest FJ, Wersto R, Arenas E, Zeng X, Freed WJ, Rao MS
NTera2 cells can be turned into dopamine-producing neurons that function like real brain cells, making them a useful tool for studying human dopamine neuron development and potential treatments for disorders like Parkinson's.
- NTera2 cells become dopamine neurons with key markers
- They respond to signals from PA6 cells to mature into functional neurons
- Selected cells show electrical activity and neurotransmitter response
- This model helps study human dopamine neuron development
- May inform therapies for NR4A2-related disorders
MSKs are required for the transcription of the nuclear orphan receptors Nur77, Nurr1 and Nor1 downstream of MAPK signalling.
Darragh J, Soloaga A, Beardmore VA, Wingate AD, Wiggin GR, Peggie M, Arthur JS
MSK kinases are essential for turning on the NR4A2 gene (Nurr1) and related genes in response to cellular signals, through a pathway involving CREB and histone modification. This process is critical for gene activation linked to brain development and function, suggesting MSKs may influence NR4A2-related disorders.
- MSK kinases control NR4A2 (Nurr1) gene activation
- MSKs act through CREB and histone changes
- This pathway responds to stress and growth signals
- Disruption may affect brain development and function
- Potential target for modulating NR4A2 activity
Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice.
Imam SZ, Jankovic J, Ali SF, Skinner JT, Xie W, Conneely OM, Le WD
Mice with one copy of the NR4A2 gene (Nurr1) show increased vulnerability to dopamine neuron damage due to higher levels of nitric oxide and related stress markers, which trigger cell death pathways. This suggests that nitric oxide contributes to the increased risk of dopamine neuron loss in NR4A2-related conditions.
- NR4A2 deficiency increases nitric oxide in brain
- Higher nitric oxide leads to cell death in dopamine neurons
- This process involves activation of apoptosis pathways
- Stress markers worsen with methamphetamine exposure
- Nitric oxide may be a target for protective treatments
Prostaglandin A2 acts as a transactivator for NOR1 (NR4A3) within the nuclear receptor superfamily.
Kagaya S, Ohkura N, Tsukada T, Miyagawa M, Sugita Y, Tsujimoto G, Matsumoto K, Saito H, Hashida R
Prostaglandin A2 activates NOR1, a nuclear receptor related to NR4A2, suggesting potential for drugs targeting this pathway in diseases like autoimmune disorders and certain cancers.
- PGA2 activates NOR1, a close relative of NR4A2
- This activation occurs through direct binding to NOR1's ligand-binding domain
- NOR1-overexpressing cells are more sensitive to PGA2
- PGA2-related compounds may offer new treatments for NOR1-related diseases
- Findings may inform therapies for NR4A2-related conditions
Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study.
Karamohamed S, Golbe LI, Mark MH, Lazzarini AM, Suchowersky O, Labelle N, Guttman M, Currie LJ, Wooten GF, Stacy M, Saint-Hilaire M, Feldman RG, Liu J, Shoemaker CM, Wilk JB, DeStefano AL, Latourelle JC, Xu G, Watts R, Growdon J, Lew M, Waters C, Vieregge P, Pramstaller PP, Klein C, Racette BA, Perlmutter JS, Parsian A, Singer C, Montgomery E, Baker K, Gusella JF, Herbert A, Myers RH
This study found no evidence that four specific genetic variants in the NR4A2 gene are linked to familial Parkinson's disease in the GenePD cohort, suggesting other genetic factors likely contribute to inherited risk.
- No NR4A2 variants found in familial Parkinson's cases
- Other genes or variants likely cause familial PD
- Results suggest NR4A2 not a major factor in this cohort
- Findings help narrow genetic causes of inherited PD
Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells.
Kim DW, Chung S, Hwang M, Ferree A, Tsai HC, Park JJ, Chung S, Nam TS, Kang UJ, Isacson O, Kim KS
Combining the Nurr1 gene with specific growth signals and stromal cells efficiently turns mouse stem cells into dopamine-producing neurons that function like those in the brain, offering a promising approach for treating Parkinson's disease.
- Nurr1 gene boosts dopamine neuron production from stem cells
- Combining Nurr1 with growth signals creates over 90% dopamine neurons
- Generated neurons act like real brain dopamine cells
- Transplanted neurons survive and integrate in brain tissue
- This method could lead to new Parkinson's cell therapies