Long-Distance Retrograde Effects of Botulinum Neurotoxin A

@article{Antonucci2008LongDistanceRE,
  title={Long-Distance Retrograde Effects of Botulinum Neurotoxin A},
  author={F. Antonucci and C. Rossi and L. Gianfranceschi and O. Rossetto and M. Caleo},
  journal={The Journal of Neuroscience},
  year={2008},
  volume={28},
  pages={3689 - 3696}
}
Botulinum neurotoxins (designated BoNT/A–BoNT/G) are bacterial enzymes that block neurotransmitter release by cleaving essential components of the vesicle fusion machinery. BoNT/A, which cleaves SNAP-25 (synaptosomal-associated protein of 25 kDa), is extensively exploited in clinical medicine to treat neuromuscular pathologies, facial wrinkles, and various types of pain. It is widely assumed that BoNT/A remains at the synaptic terminal and its effects are confined to the injection site. Here we… Expand

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References

SHOWING 1-10 OF 46 REFERENCES
Persistence of botulinum neurotoxin action in cultured spinal cord cells 1,2
TLDR
Results indicate that proteolytic activity associated with the BoNT/A light chain persists inside cells for >11 weeks, while recovery from BoNT /E is complete in <3 weeks, which appears to account for the persistence of serotype A action. Expand
Antiepileptic Effects of Botulinum Neurotoxin E
TLDR
BoNT/E delivery to the hippocampus is both antiictal and antiepileptogenic in experimental models of epilepsy, and prevents neuronal loss and long-term cognitive deficits associated with kainic acid seizures. Expand
The structure and mode of action of different botulinum toxins
TLDR
In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP‐25 and a protracted time course for the remodelling of treated nerve–muscle synapses. Expand
The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves
TLDR
A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations demonstrating the physiological relevance of this interaction. Expand
Effects of botulinum neurotoxin type A on abducens motoneurons in the cat: ultrastructural and synaptic alterations
TLDR
Data indicate that botulinum neurotoxin at high doses causes profound synaptic alterations in mot oneurons responsible for the effects seen in the behavior of motoneurons recorded in alert animals. Expand
Presynaptic enzymatic neurotoxins
TLDR
It is possible to envisage clinical applications of the lysophospholipid/fatty acid mixture to inhibit hyperactive superficial nerve terminals. Expand
Dose-dependent, central effects of botulinum neurotoxin type A
TLDR
It is concluded that paralysis per se is not enough to initiate axotomy-like neural responses in ocular mot oneurons, and some indications of the maximum allowable dose that can be used without the induction of unwanted side effects in the motoneuronal pool innervating the injected muscle are given. Expand
Neurotoxins affecting neuroexocytosis.
TLDR
The mechanism of action of three groups of presynaptic neurotoxins that interfere directly with the process of neurotransmitter release is reviewed, whereas presynapses acting on ion channels are not dealt with here. Expand
Botulinal neurotoxins: revival of an old killer.
TLDR
BoNTs are metalloproteinases that enter peripheral cholinergic nerve terminals, where they cleave one or two of the three core proteins of the neuroexocytosis apparatus and elicit persistent but reversible inhibition of neurotransmitter release. Expand
SV2 Is the Protein Receptor for Botulinum Neurotoxin A
TLDR
It is found that BoNT/A enters neurons by binding to the synaptic vesicle protein SV2 (isoforms A, B, and C), and SV2 acts as the protein receptor for Bo NT/A. Expand
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