ArticlePLoS biology2023
Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- β-Adducin Restrains PLA2G4A-Dependent Lysosomal Membrane Permeabilization and Neuronal Death in Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Photoperiod driven modulation of behavior, gut microbiota, and brain transcriptomics in zebrafish.Pflugers Archiv : European journal of physiology · 2026Article
- Microglial CARD19 ameliorates post-stroke neuroinflammation by stabilizing mitochondrial cristae.Neural regeneration research · 2026Article
- GPNMB modulates neutrophil extracellular trap formation: therapeutic implications for ischemic stroke.Journal of neuroinflammation · 2026Article
- Gata1-mediated Hras transcription stimulates blood-brain barrier injury in ischemic stroke through activation of the ERK pathway.Human cell · 2026Article
- The Role and Diagnostic Efficacy of the METTL14/GADD45B mCellular and molecular neurobiology · 2026Article
- RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.Journal of neuroinflammation · 2026Review
- Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review).International journal of molecular medicine · 2026Review
- Neuroprotective response against the onset of ischemic stroke by upregulation of histone H3Y99 sulfation.Cell reports. Medicine · 2026Article
- Esketamine Suppresses Astrocyte-Driven Neuroinflammation in Traumatic Brain Injury via the METTL5/c-Myc/PD-L1.Neurochemical research · 2026Article
- Nr4a1 regulates microglia overactivation-mediated neuroinflammation to ameliorate cognitive impairment in trigeminal neuralgia rats.The journal of headache and pain · 2026Article
- The Role of TNF-α in Ischemic Stroke.International journal of molecular sciences · 2026Review
- MicroRNA-Mediated Modulation of the Colony-Stimulating Factor 1 Pathway in Microglial Activation and Neuropathic Pain: A Next-Generation Sequencing-Based Transcriptomic Study.Pain research & management · 2026Article
- Proteoglycan 4 attenuates ischemic post-stroke hemorrhagic transformation and blood-brain barrier disruption.IBRO neuroscience reports · 2025Article
- Microglial NLRC5 drives lysosomal dysfunction to disrupt autophagic flux and promote post-stroke neuroinflammation.Journal of neuroinflammation · 2025Article
- Nr4a1 modulates inflammation and heart regeneration in zebrafish.Development (Cambridge, England) · 2025Article
- Genome-Wide Identification of Microglia-Related RNA-Binding Proteins and Regulated Alternative Splicing in Spinal Cord Injury.ACS omega · 2025Article
- Review
- Salidroside Exerts Neuroprotective Effects via Inhibiting Ferroptosis in Mice with Traumatic Brain Injury.Neurochemical research · 2025Article
- MeCP2 Lactylation Protects against Ischemic Brain Injury by Transcriptionally Regulating Neuronal Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive. Here, we observed that NR4A1 is up-regulated in the cytoplasm of activated microglia and localizes to processing bodies (P-bodies). In addition, we found that cytoplasmic NR4A1 functions as an RNA-binding protein (RBP) that directly binds and destabilizes Tnf mRNA in an N6-methyladenosine (m6A)-dependent manner. Remarkably, conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens outcomes in a mouse model of ischemic stroke, in which case NR4A1 expression is significantly induced in the cytoplasm of microglia. Thus, our study illustrates a novel mechanism that NR4A1 posttranscriptionally regulates Tnf expression in microglia and determines stroke outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.