ArticleInfection and immunity2000
Inhibition of vesicular secretion in both neuronal and nonneuronal cells by a retargeted endopeptidase derivative of Clostridium botulinum neurotoxin type A.
Article in Infection and immunity, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 64 citations in OpenAlex.
- Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications.Toxins · 2024Review
- Article
- Harnessing the Membrane Translocation Properties of AB Toxins for Therapeutic Applications.Toxins · 2021Review
- Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development.Toxins · 2020Review
- Therapeutic use of botulinum toxin in pain treatment.Neuronal signaling · 2018Review
- Review
- Selective Manipulation of Neural Circuits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Review
- Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.Scientific reports · 2016Article
- The C-terminal heavy-chain domain of botulinum neurotoxin a is not the only site that binds neurons, as the N-terminal heavy-chain domain also plays a very active role in toxin-cell binding and interactions.Infection and immunity · 2015Article
- Efficacy and safety of serial injections of botulinum toxin A in children with spastic cerebral palsy.World journal of pediatrics : WJP · 2013Article
- Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells.Journal of neurochemistry · 2013Article
- Clinical uses of botulinum neurotoxins: current indications, limitations and future developments.Toxins · 2012Review
- A botulinum toxin-derived targeted secretion inhibitor downregulates the GH/IGF1 axis.The Journal of clinical investigation · 2012Article
- Review
- Review
- Review
- Botulinum toxin for pain.Drugs in R&D · 2008Review
- Re-engineering the target specificity of Clostridial neurotoxins - a route to novel therapeutics.Neurotoxicity research · 2006Article
- Botulinum neurotoxin structure, engineering, and novel cellular trafficking and targeting.Neurotoxicity research · 2006Review
- Botulinum toxins--cause of botulism and systemic diseases?Veterinary research communications · 2005Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridial neurotoxins potently and specifically inhibit neurotransmitter release in defined cell types by a mechanism that involves cleavage of specific components of the vesicle docking/fusion complex, the SNARE complex. A derivative of the type A neurotoxin from Clostridium botulinum (termed LH(N)/A) that retains catalytic activity can be prepared by proteolysis. The LH(N)/A, however, lacks the putative native binding domain (H(C)) of the neurotoxin and is thus unable to bind to neurons and effect inhibition of neurotransmitter release. Here we report the chemical conjugation of LH(N)/A to an alternative cell-binding ligand, wheat germ agglutinin (WGA). When applied to a variety of cell lines, including those that are ordinarily resistant to the effects of neurotoxin, WGA-LH(N)/A conjugate potently inhibits secretory responses in those cells. Inhibition of release is demonstrated to be ligand mediated and dose dependent and to occur via a mechanism involving endopeptidase-dependent cleavage of the natural botulinum neurotoxin type A substrate. These data confirm that the function of the H(C) domain of C. botulinum neurotoxin type A is limited to binding to cell surface moieties. The data also demonstrate that the endopeptidase and translocation functions of the neurotoxin are effective in a range of cell types, including those of nonneuronal origin. These observations lead to the conclusion that a clostridial endopeptidase conjugate that can be used to investigate SNARE-mediated processes in a variety of cells has been successfully generated.
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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.