ArticleProceedings of the National Academy of Sciences of the United States of America2009
Bimodal modulation of the botulinum neurotoxin protein-conducting channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 89 citations in OpenAlex.
- Article
- Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Toosendanin Alleviates Cerebral Ischemia/Reperfusion Injury via Inhibiting Neural Ferroptosis Through Lipid Metabolic Reprogramming in MCAO Mice.CNS neuroscience & therapeutics · 2026Article
- Article
- Botulinum neurotoxins A, B, C, E, and F preferentially enter cultured human motor neurons compared to other cultured human neuronal populations.FEBS letters · 2019Article
- Strategies to Counteract Botulinum Neurotoxin A: Nature's Deadliest Biomolecule.Accounts of chemical research · 2019Article
- Article
- Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.Pharmacological reviews · 2017Review
- Cellular Protection of SNAP-25 against Botulinum Neurotoxin/A: Inhibition of Thioredoxin Reductase through a Suicide Substrate Mechanism.Journal of the American Chemical Society · 2016Article
- A Novel Inhibitor Prevents the Peripheral Neuroparalysis of Botulinum Neurotoxins.Scientific reports · 2015Article
- In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5.Toxicon : official journal of the International Society on Toxinology · 2015Article
- Current status and future directions of botulinum neurotoxins for targeting pain processing.Toxins · 2015Review
- Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin.Scientific reports · 2015Article
- Human Induced Pluripotent Stem Cell Derived Neuronal Cells Cultured on Chemically-Defined Hydrogels for Sensitive In Vitro Detection of Botulinum Neurotoxin.Scientific reports · 2015Article
- Inhibiting Microbial Toxins Using Plant-Derived Compounds and Plant Extracts.Medicines (Basel, Switzerland) · 2015Review
- SRC family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons.Neurotoxicity research · 2015Article
- Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity.PloS one · 2015Article
- Article
- A high content imaging assay for identification of Botulinum neurotoxin inhibitors.Journal of visualized experiments : JoVE · 2014Article
- Redox regulation of botulinum neurotoxin toxicity: therapeutic implications.Trends in molecular medicine · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Clostridium botulinum neurotoxin (BoNT) is the causative agent of botulism, a neuroparalytic disease. We describe here a semisynthetic strategy to identify inhibitors based on toosendanin, a traditional Chinese medicine reported to protect from BoNT intoxication. Using a single molecule assay of BoNT serotypes A and E light chain (LC) translocation through the heavy chain (HC) channel in neurons, we discovered that toosendanin and its tetrahydrofuran analog selectively arrest the LC translocation step of intoxication with subnanomolar potency, and increase the unoccluded HC channel propensity to open with micromolar efficacy. The inhibitory profile on LC translocation is accurately recapitulated in 2 different BoNT intoxication assays, namely the mouse protection and the primary rat spinal cord cell assays. Toosendanin has an unprecedented dual mode of action on the protein-conducting channel acting as a cargo-dependent inhibitor of translocation and as cargo-free channel activator. These results imply that the bimodal modulation by toosendanin depends on the dynamic interactions between channel and cargo, highlighting their tight interplay during the progression of LC transit across endosomes.
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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.