Research publications
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Understanding NURR1, including in relation to neurodegeneration and neuroprotection
NURR1 deficiency is associated to altered microglial phenotype in male mice
Montarolo, F et al (2025) in Molecular Neurobiology.
This study investigates the role of NURR1 in microglial function within the central nervous system (CNS).
Advances in NURR1-regulated neuroinflammation associated with Parkinson’s Disease
Al-Nusaif, M. et al (2022) in International Journal of Molecular Sciences.
This review discusses how NURR1 modulates neuroinflammation in PD, highlighting its role in suppressing inflammatory gene expression in microglia and astrocytes, and its potential as a therapeutic target.
The Role of NURR1 in metabolic abnormalities of Parkinson’s Disease
Al-Nusaif, M. et al (2022) in Molecular Neurodegeneration.
This study explores how Nurr1 influences metabolic processes in dopaminergic neurons, particularly in the context of Parkinson’s Disease, and its potential as a therapeutic target.
Willems, S. et al (2022) in Journal of Medicinal Chemistry.
This review discusses the structural and functional characteristics of Nurr1, highlighting its neuroprotective and anti-inflammatory properties. It also summarises known small molecule Nurr1 ligands and their therapeutic potential.
Moon, M. et al (2019) in Aging Cell.
This study demonstrates that NURR1 is predominantly expressed in neurons rather than glial cells. It suggests that NURR1 plays a significant role in regulating Alzheimer’s disease-related pathogenesis and cognitive function.
Montarolo, F. et al (2016) in Neurotox Res.
All three NR4A genes exhibited significantly reduced expression levels in PD patients, which suggests that the whole NR4A subfamily may play a role in the pathogenesis of PD and could serve as potential biomarkers for disease diagnosis or progression. In Alzheimers, only NR4A1 levels were notably decreased.
Nurr1 reduction influences the onset of chronic EAE in mice
Montarolo, F. et al (2015) in Inflamm Res.
This study investigates the role of Nurr1 in the onset and progression of experimental autoimmune encephalomyelitis (EAE) and found that reducing NURR1 expression leads to earlier onset. The immune response against myelin in the mice, a hallmark of MS, becomes more pronounced, which accelerates disease progression.
a-synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons
Decressac, M. et al (2012) in Sci Transl Med.
This article explores how alpha-synuclein accumulation leads to decreased NURR1 expression, impairing GDNF signalling and contributing to dopaminergic neuron degeneration.
Nurr1 transcriptionally regulates the expression of alpha-synuclein
Yang, Y.X. et al (2008) in Neuroreport.
This research identifies that reduced NURR1 expression leads to increased alpha-synuclein levels, suggesting a link between NURR1 dysfunction and PD pathogenesis.
Smith, G.A. et al (2015) in PLOS ONE.
This study evaluates a NURR1 agonist, SA00025, demonstrating its ability to induce dopaminergic gene expression and provide neuroprotection in an inflammation-exacerbated PD model.
Decreased NURR1 gene expression in patients with Parkinson’s Disease
Le, W. et al (2008) in J Neurol Sci.
NURR1 gene expression was significantly decreased in patients with Parkinson’s Disease, both with and without medication.
Nurr1 in Parkinson’s Disease and related disorders
Chu, Y. et al (2006) in J Comp Neurol.
It is demonstrated that Nurr1 deficiency in dopaminergic neurone is associated with intracellular pathology in both synucleinopathies and tauopathies.
Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra
Chu, Y. et al (2002) in J Comp Neurol.
Stereologic counts revealed a significant reduction in the number of Nurr1-ir nigral neurons in middle aged (23.13%) and aged (46.33%) relative to young subjects.
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Understanding clinical phenotype(s) including NR4A2-related disorder
Expanding the clinical spectrum of NR4A2-related disorder: A systematic literature review and case series
Borden, C. et al (2025), in American Journal of Medical Genetics.
This study also presents two novel cases, expanding the clinical spectrum to include reactive hypoglycaemia, cystic kidney disease and joint hyper mobility.
NURR1-deficient mice have age - and sex- specific behavioural phenotypes
Montarolo, F. et al (2022), in Journal of Neuroscience Resesarch.
The study concludes that NURR1 plays a critical role in modulating behaviour, and deficiency leads to different phenotypes depending on sex and age. This suggests potential implications for understanding dopaminergic dysfunction in neurodegenerative diseases.
Ruiz-Sanchez, E. et al (2021) in BMC Psychiatry.
Findings suggest that changes in NR4A2 expression levels could be associated with working memory in schizophrenia depending on genotype in a sample from a Mexican population.
Loss-of-function mutations in NR4A2 cause Dopa-responsive dystonia Parkinsonism
Wirth, T. et al (2020), in Movement Disorders.
Two patients reported here had mild intellectual disability in childhood and subsequently developed dystonia Parkinsonism in early adulthood. MRIs were normal, and DATscan suggested bilateral dopaminergic denervation. Two frameshift mutations (insertions) were identified.
De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy
Singh, S. et al (2020) in Genetics in Medicine.
Nine patients with NR4A2 mutations associated with developmental delay, hypotonia and epilepsy in six cases. The findings suggest the role of NR4A2 as a critical gene in neurodevelopment and seizure regulation.
NURR1 deficiency is associated to ADHD-like phenotypes in mice
Montarolo, F. et al (2019), in Translational Psychiatry.
NURR1 is involved in regulating dopamine which is a key neurotransmitter implicated in ADHD. The study concludes that NURR1 deficiency plays a significant role in the etiology of ADHD and understanding NURR1’s role could open up new avenues for personalised treatments.
Guo, H et al. (2019) in Genetics in Medicine.
This wider study included one patient with a de novo frameshift variant in NR4A2 and autism symptoms. Overall, the study concluded that patients with more than one risk variant were more severely affected than patients with a single or no-risk variant.
Ramos, L.L.P et al (2019) in Clin Case Rep.
This case study highlights a patient with a de novo loss-of-function NR4A2 variation and reinforces the role of NR4A2 in neurodevelopmental phenotypes.
NR4A2 haploinsufficiency is associated with intellectual disability and autism spectrum disorder
Levy, J. et al (2018) in Clin Genet.
This report describes three additional patients with de novo deletions including NR4A2, presenting with language impairment, developmental delay, intellectual disability and / or autism spectrum disorder.
Reuter, M.S. et al (2017), in American Journal of Medical Genetics.
This study reports a patient with a deletion of NR4A2, leading to mild intellectual disability and significant speech and language impairment. The findings support NR4A2 haploinsuffiency as a cause for neurodevelopmental disorders, particularly affecting language development.
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Potential for treatments to increase NURR1 (small molecules and gene therapies)
A Nurr1 agonist derived from the natural ligand DHI induces neuroprotective gene expression
Egner, M. et al (2025) in Journal of Medicinal Chemistry.
Nurr1 modulators - a patent review (2019-present)
Egner, M. et al (2025) in Expert Opinion Ther Pat.
This paper discusses NURR1 modulation as an emerging therapeutic concept and considers several promising compounds covered by patent applications.
Yang, Y. et al (2023) in Mol Psychiatry.
A series of functional, histologic and transcriptome analyses revealed that the combined expression of Nurr1 and Foxa2 substantially ameliorated AD-associated amyloid and Tau proteinopathy, cell senescence, synaptic loss and neuro-inflammation.
An optimized Nurr1 agonist provides disease-modifying effects in Parkinson’s disease
Kim, W. et al (2023), in Nat Commun.
An optimised agonist of Nurr1, 4A7C-301, protects dopamine neurons in vitro, and improves both motor and non-motor deficits in male rodent models of PD.
Development of a potent Nurr1 agonist tool for in vivo applications
Vietor, J. et al (2023) in Journal of Medicinal Chemistry.
The optimized compound induced Nurr1-regulated gene expression in astrocytes and exhibited favourable pharmokinetics in rats, emerging as a superior chemical tool to study Nurr1 activation.
Assessment of NR4A ligands that directly bind and modulate the orphan nuclear receptor Nurr1
Aldhafiri, S. et al (2023) in Journal of Medicinal Chemistry.
An in-depth analysis of NR4A ligands, including C-DIM12, and their interactions with Nurr1, highlighting their potential in treating neurodegenerative diseases.
Aldhafiri, S. et al (2023) in Receptors.
This article discusses the effects of C-DIM12, a compound that activates NR4 receptors, on inflammatory mediators in myeloid cells. It suggests that C-DIM12 could be a potential therapeutic agent for modulating immune responses via NR4A2.
Guttuso, T. et al (2023) in IBRO Neuroscience Rep.
The trial provides preliminary evidence supporting lithium’s potential effects, which aligns with previous research suggesting that lithium may influence neuroprotective pathways and disease progression in neurodegenerative conditions.
Catala-Solsona, J. et at (2023) in J Neurosci.
This study provides mechanistic insights into the molecular pathways related to hippocampus synaptic plasticity and learning, and also identifies Nr4a2 as a potential therapeutic target for conditions associated with dysregulation of glutamtergic synaptic function.
PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function
Rajan, S. et al (2020) in Nat Chem Biol.
The paper demonstrates that PGE1 and PGA1 can bind to Nurr1, using techniques like binding assays and structural analysis. It opens up possibilities for targeting prostaglandin receptors or manipulating prostaglandin-Nurr1 interaction to restore or protect dopaminergic neurons.
Pharmacological activation of Nr4a rescues age-associated memory decline
Chatterjee, S. et al (2019), Neurobiology of Aging
This study investigates the role of Nr4a2 in memory formation and its potential as a therapeutic target for age-related cognitive decline.
Study of the NR4A family gene expression in patients with multiple sclerosis treated with Fingolimod
Montarolo, F. et al (2019) in European Journal of Neurology.
Patients treated with Fingolimod for >2 years in this preclinical study were characterised by higher levels of NR4A2, approaching those of healthy controls.
Selective brain penetrable Nurr1 transactivator for treating Parkinson’s Disease
Wang, J. et al (2016) in Oncotarget.
This study suggests that IRX4204 is a novel, potent and selective pharmacological means to activate cellular RXR-Nurr1 signalling and promote dopaminergic neuron survival in PD.
Nurr1-based therapies for Parkinson’s Disease
Dong, J. et al (2016) in CNS Neuroscience Ther.
This review highlights the progress in preclinical studies of Nurr1-based therapies and discusses this emerging therapy as a promising new generation of PD medication.
Current pharmaceutical treatments and alternative therapies of Parkinson’s Disease
Dong, J. et al (2016) in Curr Neuropharmacol.
This review article provides a comprehensive review of established and emerging therapies for PD.
Crean, D. et al (2015) in The Journal of Immunology.
This study explores how adenosine and its receptor agonists can modulate NR4A receptors, including NR4A2, to reduce hyper inflammatory responses in monocytic cells. It suggests that targeting NR4A2 may be beneficial for inflammatory conditions.