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Related Concept Videos

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The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
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Nondepolarizing neuromuscular blockers prevent the membrane depolarization of muscle cells and inhibit muscle contraction. These are usually administered with anesthetics to achieve complete muscle relaxation. Upon administration, these drugs first block the small, rapidly contracting muscles of the face and hands, followed by the larger muscles of the trunk and the intercostal muscles. The diaphragm is the last muscle to be affected.
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Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
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A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
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Novel Native and Engineered Botulinum Neurotoxins.

Lance Steward1, Mitchell F Brin1,2, Amy Brideau-Andersen3

  • 1Allergan plc, Irvine, CA, USA.

Handbook of Experimental Pharmacology
|April 11, 2020
PubMed
Summary

Botulinum neurotoxins (BoNTs) are potent bacterial toxins that cause paralysis by blocking neurotransmitter release. Researchers are developing novel recombinant BoNTs for therapeutic and diagnostic applications.

Keywords:
AbobotulinumtoxinABotulinum toxinIncobotulinumtoxinANeurotoxinOnabotulinumtoxinAPrabotulinumtoxinA-xvfsRecombinantRimabotulinumtoxinB

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Area of Science:

  • Molecular Biology
  • Neuroscience
  • Toxicology

Background:

  • Botulinum neurotoxins (BoNTs) are highly potent toxins produced by bacteria, known for causing muscle paralysis.
  • BoNTs function by cleaving SNARE proteins, inhibiting neurotransmitter release from neurons.
  • The mechanism of BoNTs has led to therapeutic and cosmetic applications.

Purpose of the Study:

  • To provide an overview of native BoNTs, including classical, mosaic, and newly identified strains.
  • To explore the potential of recombinant BoNTs derived from modular toxin structures.
  • To highlight the diverse applications of novel BoNTs in research and medicine.

Main Methods:

  • Review of existing literature on native BoNT serotypes and their clinical uses.
  • Analysis of the modular structure (light and heavy chains) of BoNTs.
  • Exploration of molecular biology techniques for creating novel recombinant BoNTs.

Main Results:

  • Identification and classification of classical, mosaic, and novel BoNTs from various bacterial sources.
  • Demonstration of the amenability of BoNTs to genetic modification for creating recombinant variants.
  • Emerging applications of recombinant BoNTs in toxin research, vaccine development, and targeted drug delivery.

Conclusions:

  • Native BoNTs represent a significant class of potent neurotoxins with established clinical uses.
  • Recombinant BoNTs offer versatile platforms for advancing scientific understanding and developing innovative therapeutics.
  • The potential applications of engineered BoNTs extend to neuronal and non-neuronal targets, promising new treatment strategies.