Abstract
The clostridial neurotoxins (CNTs) are among the most potent protein toxins known to humans. CNTs include seven serotypes (A~G) of botulinum toxins (BoNTs), which cause botulism, a flaccid paralysis, and tetanus toxin (TeNT), which causes spastic paralysis. BoNTs are classified as category A agent and may be used as potential bioterrorism weapons. On the other hand, the ability of an extremely low dosage of BoNTs (less than 1 ng) to cause reversible partial paralysis upon injection into muscle has turned BoNTs, in particular serotypes A and B, from deadly agents to novel therapeutic agents for treatment of a wide range of clinical conditions associated with involuntary muscle spasm and contractions. In addition to clinical use, they may also be used in cosmetics. Further indications for BoNTs will continue to be developed, although current BoNT therapies have encountered some limitations due to the pharmacological properties of BoNTs, such as their ability to elicit immunoresistance in patients upon periodical injections. This review summarizes the present knowledge of the mechanisms of action of CNTs, with particular focus on the mode of substrate recognition by CNT catalytic domains and knowledge regarding substrate recognition can be utilized to develop novel BoNT products to extend its usefulness in therapeutic interventions and overcome the immunoresistance problems.
Keywords: Botulinum toxins (BoNTs), Clostridial neurotoxins (CNTs), novel therapy development, substrate recognition.
Current Protein & Peptide Science
Title:Clostridial Neurotoxins: Mode of Substrate Recognition and Novel Therapy Development
Volume: 15 Issue: 5
Author(s): Sheng Chen
Affiliation:
Keywords: Botulinum toxins (BoNTs), Clostridial neurotoxins (CNTs), novel therapy development, substrate recognition.
Abstract: The clostridial neurotoxins (CNTs) are among the most potent protein toxins known to humans. CNTs include seven serotypes (A~G) of botulinum toxins (BoNTs), which cause botulism, a flaccid paralysis, and tetanus toxin (TeNT), which causes spastic paralysis. BoNTs are classified as category A agent and may be used as potential bioterrorism weapons. On the other hand, the ability of an extremely low dosage of BoNTs (less than 1 ng) to cause reversible partial paralysis upon injection into muscle has turned BoNTs, in particular serotypes A and B, from deadly agents to novel therapeutic agents for treatment of a wide range of clinical conditions associated with involuntary muscle spasm and contractions. In addition to clinical use, they may also be used in cosmetics. Further indications for BoNTs will continue to be developed, although current BoNT therapies have encountered some limitations due to the pharmacological properties of BoNTs, such as their ability to elicit immunoresistance in patients upon periodical injections. This review summarizes the present knowledge of the mechanisms of action of CNTs, with particular focus on the mode of substrate recognition by CNT catalytic domains and knowledge regarding substrate recognition can be utilized to develop novel BoNT products to extend its usefulness in therapeutic interventions and overcome the immunoresistance problems.
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Cite this article as:
Chen Sheng, Clostridial Neurotoxins: Mode of Substrate Recognition and Novel Therapy Development, Current Protein & Peptide Science 2014; 15 (5) . https://dx.doi.org/10.2174/13892037113146660086
DOI https://dx.doi.org/10.2174/13892037113146660086 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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