Abstract
Botulinum neurotoxins produced by various Clostridium sp are the most potent acute lethal toxins known, and yet they have found increasing use in the clinical treatment of diseases or conditions involving neuromuscular or autonomic neuronal transmission. By a process involving proteolytic cleavage of one or more SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, botulinum toxins inhibit the release of acetylcholine from peripheral cholinergic nerve terminals. Cleavage of SNARE proteins is both specific and effective, and leads to blockade of secretory vesicle fusion that is maintained for many weeks or months. Though inhibition of release of transmitter is currently the most clinically-relevant endpoint, SNARE proteolysis can also inhibit presentation of receptors, channels and other surface-membrane located materials. The implications for signal transduction are only just becoming apparent, but are an important facet of the mechanism of action of botulinum neurotoxins. Additionally, the ubiquitous distribution of the SNARE proteins ensures that proteolysis-dependent inhibition of transmitter release and receptor/channel presentation is theoretically not confined to neuronal targets. This review will consider the potential of botulinum neurotoxins as inhibitors of intercellular communication, and highlight the general concept of deriving novel therapeutic molecules from the neurotoxins.
Keywords: Clostridium, botulinum toxin, SNARE, exocytosis, neurotoxin
Current Signal Transduction Therapy
Title: Manipulation of Signal Transduction by Botulinum Neurotoxins and their Derivatives
Volume: 2 Issue: 3
Author(s): John A. Chaddock and Keith A. Foster
Affiliation:
Keywords: Clostridium, botulinum toxin, SNARE, exocytosis, neurotoxin
Abstract: Botulinum neurotoxins produced by various Clostridium sp are the most potent acute lethal toxins known, and yet they have found increasing use in the clinical treatment of diseases or conditions involving neuromuscular or autonomic neuronal transmission. By a process involving proteolytic cleavage of one or more SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, botulinum toxins inhibit the release of acetylcholine from peripheral cholinergic nerve terminals. Cleavage of SNARE proteins is both specific and effective, and leads to blockade of secretory vesicle fusion that is maintained for many weeks or months. Though inhibition of release of transmitter is currently the most clinically-relevant endpoint, SNARE proteolysis can also inhibit presentation of receptors, channels and other surface-membrane located materials. The implications for signal transduction are only just becoming apparent, but are an important facet of the mechanism of action of botulinum neurotoxins. Additionally, the ubiquitous distribution of the SNARE proteins ensures that proteolysis-dependent inhibition of transmitter release and receptor/channel presentation is theoretically not confined to neuronal targets. This review will consider the potential of botulinum neurotoxins as inhibitors of intercellular communication, and highlight the general concept of deriving novel therapeutic molecules from the neurotoxins.
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Cite this article as:
Chaddock A. John and Foster A. Keith, Manipulation of Signal Transduction by Botulinum Neurotoxins and their Derivatives, Current Signal Transduction Therapy 2007; 2 (3) . https://dx.doi.org/10.2174/157436207781745382
DOI https://dx.doi.org/10.2174/157436207781745382 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
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