ArticleGlia2022
SRI-42127, a novel small molecule inhibitor of the RNA regulator HuR, potently attenuates glial activation in a model of lipopolysaccharide-induced neuroinflammation.
Article in Glia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- FAM120A - a protein inserted in the ALS disease network.Scientific reports · 2026Article
- ELAV/Hu RNA-binding protein family: key regulators in neurological disorders, cancer, and other diseases.RNA biology · 2025Review
- Myeloid-specific tristetraprolin mitigates postsurgical incisional pain by suppressing proinflammatory responses.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Myeloid-specific Tristetraprolin mitigates postsurgical incisional pain by suppressing proinflammatory responses.Research square · 2025Article
- The Roles of RNA-Binding Proteins in Vasculogenic Mimicry Regulation in Glioblastoma.International journal of molecular sciences · 2025Review
- Inhibition of the RNA Regulator HuR Mitigates Spinal Cord Injury by Potently Suppressing Post-Injury Neuroinflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Structural, biological, and biomedical implications of mRNA interactions with the master regulator HuR.NAR molecular medicine · 2025Review
- Post-transcriptional regulation by HuR in colorectal cancer: impacts on tumor progression and therapeutic strategies.Frontiers in immunology · 2025Review
- CRISPR/Cas9-Mediated Knockout of theMicroorganisms · 2024Article
- Review
- Emerging roles of RNA binding proteins in intervertebral disc degeneration and osteoarthritis.Orthopaedic surgery · 2023Review
- A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation.Nature communications · 2023Article
- HuR modulation counteracts lipopolysaccharide response in murine macrophages.Disease models & mechanisms · 2023Article
- Inhibition of the RNA Regulator HuR by SRI-42127 Attenuates Neuropathic Pain After Nerve Injury Through Suppression of Neuroinflammatory Responses.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.Advanced drug delivery reviews · 2022Review
- Targeting the TREM1-positive myeloid microenvironment in glioblastoma.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Glial activation with the production of pro-inflammatory mediators is a major driver of disease progression in neurological processes ranging from acute traumatic injury to chronic neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. Posttranscriptional regulation is a major gateway for glial activation as many mRNAs encoding pro-inflammatory mediators contain adenine- and uridine-rich elements (ARE) in the 3' untranslated region which govern their expression. We have previously shown that HuR, an RNA regulator that binds to AREs, plays a major positive role in regulating inflammatory cytokine production in glia. HuR is predominantly nuclear in localization but translocates to the cytoplasm to exert a positive regulatory effect on RNA stability and translational efficiency. Homodimerization of HuR is necessary for translocation and we have developed a small molecule inhibitor, SRI-42127, that blocks this process. Here we show that SRI-42127 suppressed HuR translocation in LPS-activated glia in vitro and in vivo and significantly attenuated the production of pro-inflammatory mediators including IL1β, IL-6, TNF-α, iNOS, CXCL1, and CCL2. Cytokines typically associated with anti-inflammatory effects including TGF-β1, IL-10, YM1, and Arg1 were either unaffected or minimally affected. SRI-42127 suppressed microglial activation in vivo and attenuated the recruitment/chemotaxis of neutrophils and monocytes. RNA kinetic studies and luciferase studies indicated that SRI-42127 has inhibitory effects both on mRNA stability and gene promoter activation. In summary, our findings underscore HuR's critical role in promoting glial activation and the potential for SRI-42127 and other HuR inhibitors for treating neurological diseases driven by this activation.
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Registered trials
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.