ArticleEMBO reports2022
Myeloid cell-specific topoisomerase 1 inhibition using DNA origami mitigates neuroinflammation.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Interactions of the DNA Nanostructure with Silane-Based Self-Assembled Monolayers.Langmuir : the ACS journal of surfaces and colloids · 2026Article
- Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease.Genome research · 2026Article
- TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration.Nature neuroscience · 2026Article
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Resolving DNA origami structural integrity and pharmacokinetics in vivo.Nature nanotechnology · 2026Article
- The Function of Microglia in Cognitive Impairment Influenced by Sleep Deprivation.Cellular and molecular neurobiology · 2026Review
- Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications.Biomedicines · 2026Review
- Single-cell transcriptomics of neuroinflammation and cerebrovascular endothelial cells in the aged rat hippocampus.iScience · 2025Article
- Neopterin mediates sleep deprivation-induced microglial activation resulting in neuronal damage by affecting YY1/HDAC1/TOP1/IL-6 signaling.Journal of advanced research · 2025Article
- Therapeutic potential of microglial SMEK1 in regulating H3K9 lactylation in cerebral ischemia-reperfusion.Communications biology · 2024Article
- Role of immune cell interactions in alcohol-associated liver diseases.Liver research (Beijing, China) · 2024Review
- Spinal Cord Injury Management Based on Microglia-Targeting Therapies.Journal of clinical medicine · 2024Review
- A pharmacological toolkit for human microglia identifies Topoisomerase I inhibitors as immunomodulators for Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome.Molecular neurodegeneration · 2023Article
- Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function.Acta pharmacologica Sinica · 2023Article
- Microglial aryl hydrocarbon receptor enhances phagocytic function via SYK and promotes remyelination in the cuprizone mouse model of demyelination.Journal of neuroinflammation · 2023Article
- Topoisomerases in Immune Cell Development and Function.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Signature-Based Computational Drug Repurposing for Amyotrophic Lateral Sclerosis.Advances in experimental medicine and biology · 2023Article
- Activated microglia release β-galactosidase that promotes inflammatory neurodegeneration.Frontiers in aging neuroscience · 2023Article
- Myeloid cell-specific topoisomerase 1 inhibition using DNA origami mitigates neuroinflammation.EMBO reports · 2022Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting myeloid cells, especially microglia, for the treatment of neuroinflammatory diseases such as multiple sclerosis (MS), is underappreciated. Our in silico drug screening reveals topoisomerase 1 (TOP1) inhibitors as promising drug candidates for microglial modulation. We show that TOP1 is highly expressed in neuroinflammatory conditions, and TOP1 inhibition using camptothecin (CPT) and its FDA-approved analog topotecan (TPT) reduces inflammatory responses in microglia/macrophages and ameliorates neuroinflammation in vivo. Transcriptomic analyses of sorted microglia from LPS-challenged mice reveal an altered transcriptional phenotype following TPT treatment. To target myeloid cells, we design a nanosystem using β-glucan-coated DNA origami (MyloGami) loaded with TPT (TopoGami). MyloGami shows enhanced specificity to myeloid cells while preventing the degradation of the DNA origami scaffold. Myeloid-specific TOP1 inhibition using TopoGami significantly suppresses the inflammatory response in microglia and mitigates MS-like disease progression. Our findings suggest that TOP1 inhibition in myeloid cells represents a therapeutic strategy for neuroinflammatory diseases and that the myeloid-specific nanosystems we designed may also benefit the treatment of other diseases with dysfunctional myeloid cells.
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