ArticleThe Journal of experimental medicine2023
A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation.
Article in The Journal of experimental medicine, 2023. 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, 26 citations in OpenAlex.
- Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Article
- Lymphoid-like Suppressive Microglia in Alzheimer's Disease: A New Neuroimmune Regulatory Axis?Cells · 2026Review
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Immune receptor LAG3 regulates microglia function during Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Flipping the Switch: MeCP2-Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- lncRNAbioRxiv : the preprint server for biology · 2025Article
- M2-exo promote orthodontic bone remodeling via the MeCP2-TCF20-HDAC1 axis.Stem cell research & therapy · 2025Article
- Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals.eLife · 2025Article
- Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.The journal of headache and pain · 2025Article
- HDAC1 Promotes Hippocampal Neuronal Pyroptosis in Epileptic Mice Through the miR-15a-5p/Caspase-1 Axis.Neurochemical research · 2025Article
- Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs.Frontiers in immunology · 2025Review
- Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.Frontiers in cellular neuroscience · 2025Review
- Analysis of LINC00472 as a biomarker of osteoarthritis and its clinical value.Archives of rheumatology · 2024Article
- Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.Nature genetics · 2024Article
- Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.Epigenomics · 2024Review
- Established and emerging techniques for the study of microglia: visualization, depletion, and fate mapping.Frontiers in cellular neuroscience · 2024Review
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Pervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer's disease (AD). SPI1/PU.1 is a transcription factor located at a genome-wide significant AD-risk locus and its reduced expression is associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia of human AD patients and found an enrichment of PU.1-binding motifs in the differentially expressed genes. In hippocampal tissues from transgenic mice with neurodegeneration, we found vastly increased genomic PU.1 binding. We then screened for PU.1 inhibitors using a PU.1 reporter cell line and discovered A11, a molecule with anti-inflammatory efficacy and nanomolar potency. A11 regulated genes putatively by recruiting a repressive complex containing MECP2, HDAC1, SIN3A, and DNMT3A to PU.1 motifs, thus representing a novel mechanism and class of molecules. In mouse models of AD, A11 ameliorated neuroinflammation, loss of neuronal integrity, AD pathology, and improved cognitive performance. This study uncovers a novel class of anti-inflammatory molecules with therapeutic potential for neurodegenerative disorders.
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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.