ArticlePloS one2011
Accelerated neuronal cell recovery from Botulinum neurotoxin intoxication by targeted ubiquitination.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Comprehensive Mapping of Immune Nanobody Repertoires with NanoMAP.bioRxiv : the preprint server for biology · 2026Article
- Nanobody-Functionalized Magnetic Beads for Enrichment of Foodborne Botulinum Toxin Type A Light Chain.Journal of microbiology and biotechnology · 2025Article
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- The Degradation of Botulinum Neurotoxin Light Chains Using PROTACs.International journal of molecular sciences · 2024Article
- Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023Review
- Single Domain Antibody application in bacterial infection diagnosis and neutralization.Frontiers in immunology · 2022Review
- A Nanobody-Based Toolset to Monitor and Modify the Mitochondrial GTPase Miro1.Frontiers in molecular biosciences · 2022Article
- Neuronal delivery of antibodies has therapeutic effects in animal models of botulism.Science translational medicine · 2021Article
- Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity.Frontiers in pharmacology · 2021Article
- An Inside Job: Applications of Intracellular Single Domain Antibodies.Biomolecules · 2020Review
- Endocytosis, trafficking and exocytosis of intact full-length botulinum neurotoxin type a in cultured rat neurons.Neurotoxicology · 2020Article
- Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.Pharmacological reviews · 2020Review
- Antibodies and venom peptides: new modalities for ion channels.Nature reviews. Drug discovery · 2019Review
- Using Nanobodies to Study Protein Function in Developing Organisms.Antibodies (Basel, Switzerland) · 2019Review
- Deubiquitinating enzyme VCIP135 dictates the duration of botulinum neurotoxin type A intoxication.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery.Scientific reports · 2017Article
- In Vivo Toxicity and Immunological Characterization of Detoxified Recombinant Botulinum Neurotoxin Type A.Pharmaceutical research · 2016Article
- Article
- Atoxic derivative of botulinum neurotoxin A as a prototype molecular vehicle for targeted delivery to the neuronal cytoplasm.PloS one · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Botulinum neurotoxin (BoNT), a Category A biodefense agent, delivers a protease to motor neuron cytosol that cleaves one or more soluble NSF attachment protein receptors (SNARE) proteins involved in neurotransmission to cause a flaccid paralysis. No antidotes exist to reverse symptoms of BoNT intoxication so severely affected patients require artificial respiration with prolonged intensive care. Time to recovery depends on toxin serotype because the intraneuronal persistence of the seven known BoNT serotypes varies widely from days to many months. Our therapeutic antidote strategy is to develop 'targeted F-box' (TFB) agents that target the different intraneuronal BoNT proteases for accelerated degradation by the ubiquitin proteasome system (UPS), thus promoting rapid recovery from all serotypes. These agents consist of a camelid heavy chain-only V(H) (VHH) domain specific for a BoNT protease fused to an F-box domain recognized by an intraneuronal E3-ligase. A fusion protein containing the 14 kDa anti-BoNT/A protease VHH, ALcB8, joined to a 15 kDa F-box domain region of TrCP (D5) was sufficient to cause increased ubiquitination and accelerate turnover of the targeted BoNT/A protease within neurons. Neuronal cells expressing this TFB, called D5-B8, were also substantially resistant to BoNT/A intoxication and recovered from intoxication at least 2.5 fold quicker than control neurons. Fusion of D5 to a VHH specific for BoNT/B protease (BLcB10) led to accelerated turnover of the targeted protease within neurons, thus demonstrating the modular nature of these therapeutic agents and suggesting that development of similar therapeutic agents specific to all botulinum serotypes should be readily achievable.
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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.