ArticleJournal of neuroinflammation2022
Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- The Murine Antimicrobial Peptide CRAMP Alleviates Neuroinflammation By Downregulating the cGAS-STING Signalling Pathway.Molecular neurobiology · 2026Article
- Mitochondria-Targeted Lonidamine Hydrogels for Postsurgical Elimination of Glioblastoma.Gels (Basel, Switzerland) · 2026Article
- Research Progress on Regulating Neuroinflammation After Spinal Cord Injury by Targeting the cGAS-STING Pathway.Neuromolecular medicine · 2026Review
- Decoding neuroinflammation: the critical role of NLRP3 inflammasome in Alzheimer's disease.Inflammopharmacology · 2026Review
- Inhibition of HSPA8 alleviates experimental autoimmune encephalomyelitis via dual modulation of NLRP3 inflammasome activation: suppressing both NF-κB-mediated priming and ASC-dependent assembly.Cell death discovery · 2026Article
- The ASC-c isoform as a modulator of inflammasome activation: Insights into molecular mechanisms and therapeutic applications.The Journal of biological chemistry · 2026Article
- Neuronal inflammasomes: balancing immunity, neuroinflammation, and homeostasis.Trends in immunology · 2026Review
- Host Aging Induces a Senescent-Like Phenotype in Neutrophils and Altered Transcriptional Responses to Streptococcus pneumoniae.Aging cell · 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
- Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.Mediators of inflammation · 2026Review
- Machine Learning Analysis of Cytotoxicity Determinants in Nanoparticle-Based Rheumatoid Arthritis Therapies.Molecular pharmaceutics · 2025Article
- Transcriptional and neuroprotective effects of hexokinase-2 inhibitors administered after stroke.Journal of neuroinflammation · 2025Article
- Glycolytic Enzyme HK2 Phosphorylates nSMase1 to Promote Astrocytic Exosomes Biogenesis Contributing to Acute Ischemic Stroke Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unraveling the Converging Roles of ASC-Dependent Inflammasomes, Interleukin-1 Superfamily Members, Serum Amyloid A, and Non-Sterile Inflammation in Disease Pathology and Fibrosis in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.International journal of molecular sciences · 2025Review
- Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies.MedComm · 2025Review
- Role of inflammasomes in cancer immunity: mechanisms and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025Review
- Lonidamine, a Novel Modulator for the BvgAS System of Bordetella Species.Microbiology and immunology · 2025Article
- Inflammasome components as new therapeutic targets in inflammatory disease.Nature reviews. Immunology · 2025Review
- New applications of clioquinol in the treatment of inflammation disease by directly targeting arginine 335 of NLRP3.Journal of pharmaceutical analysis · 2025Article
- The impact of glycolysis on ischemic stroke: from molecular mechanisms to clinical applications.Frontiers in neurology · 2025Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDysregulated activation of the inflammasome is involved in various human diseases including acute cerebral ischemia, multiple sclerosis and sepsis. Though many inflammasome inhibitors targeting NOD-like receptor protein 3 (NLRP3) have been designed and developed, none of the inhibitors are clinically available. Growing evidence suggests that targeting apoptosis-associated speck-like protein containing a CARD (ASC), the oligomerization of which is the key event for the assembly of inflammasome, may be another promising therapeutic strategy. Lonidamine (LND), a small-molecule inhibitor of glycolysis used as an antineoplastic drug, has been evidenced to have anti-inflammation effects. However, its anti-inflammatory mechanism is still largely unknown.
methodsMiddle cerebral artery occlusion (MCAO), experimental autoimmune encephalomyelitis (EAE) and LPS-induced sepsis mice models were constructed to investigate the therapeutic and anti-inflammasome effects of LND. The inhibition of inflammasome activation and ASC oligomerization by LND was evaluated using western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) in murine bone marrow-derived macrophages (BMDMs). Direct binding of LND with ASC was assessed using molecular mock docking, surface plasmon resonance (SPR), and drug affinity responsive target stability (DARTS).
resultsHere, we find that LND strongly attenuates the inflammatory injury in experimental models of inflammasome-associated diseases including autoimmune disease-multiple sclerosis (MS), ischemic stroke and sepsis. Moreover, LND blocks diverse types of inflammasome activation independent of its known targets including hexokinase 2 (HK2). We further reveal that LND directly binds to the inflammasome ligand ASC and inhibits its oligomerization.
conclusionsTaken together, our results identify LND as a broad-spectrum inflammasome inhibitor by directly targeting ASC, providing a novel candidate drug for the treatment of inflammasome-driven diseases in clinic.
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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.