ArticleBrain, behavior, and immunity2018
HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage.
Article in Brain, behavior, and immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
- Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.eLife · 2026Article
- The Interplay Between Nurr1 and Mitochondrial Biogenesis: Implications for Neurodegenerative Therapy.Molecular neurobiology · 2026Review
- Role of Nuclear Receptors on the Progression of Multiple Sclerosis: A Review.Cellular and molecular neurobiology · 2025Review
- Article
- BRF110, an Orally Active Nurr1-RXRα-Selective Rexinoid, Enhances BDNF Expression without Elevating Triglycerides.Journal of medicinal chemistry · 2025Article
- Article
- Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology.International journal of molecular sciences · 2023Review
- Increased fatty acid metabolism and decreased glycolysis are hallmarks of metabolic reprogramming within microglia in degenerating white matter during recovery from experimental stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Review
- Dynamic release of neuronal extracellular vesicles containing miR-21a-5p is induced by hypoxia.Journal of extracellular vesicles · 2023Article
- Advances in NURR1-Regulated Neuroinflammation Associated with Parkinson's Disease.International journal of molecular sciences · 2022Review
- The role of NURR1 in metabolic abnormalities of Parkinson's disease.Molecular neurodegeneration · 2022Review
- Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.Molecular neurobiology · 2022Review
- Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (International journal of molecular sciences · 2022Article
- Nuclear receptors of NR1 and NR4 subfamilies in the regulation of microglial functions and pathology.Pharmacology research & perspectives · 2021Review
- SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models.EMBO molecular medicine · 2021Article
- FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages.Journal of neuroinflammation · 2020Article
- Metabolome Changes in Cerebral Ischemia.Cells · 2020Review
- Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation.Journal of neuroinflammation · 2020Article
- Opposite regulation of piRNAs, rRNAs and miRNAs in the blood after subarachnoid hemorrhage.Journal of molecular medicine (Berlin, Germany) · 2020Article
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.
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