The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Long-Distance Retrograde Effects of Botulinum Neurotoxin A
Open accessAbstract
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 demonstrate that catalytically active BoNT/A is retrogradely transported by central neurons and motoneurons and is then transcytosed to afferent synapses, in which it cleaves SNAP-25. SNAP-25 cleavage by BoNT/A was observed in the contralateral hemisphere after unilateral BoNT/A delivery to the hippocampus. Appearance of cleaved SNAP-25 resulted in blockade of hippocampal activity in the untreated hemisphere. Injections of BoNT/A into the optic tectum led to the appearance of BoNT/A-truncated SNAP-25 in synaptic terminals within the retina. Cleaved SNAP-25 also appeared in the facial nucleus after injection of the toxin into rat whisker muscles. Experiments excluded passive spread of the toxin and demonstrated axonal migration and neuronal transcytosis of BoNT/A. These findings reveal a novel pathway of BoNT/A trafficking in neurons and have important implications for the clinical uses of this neurotoxin.
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Cites
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Neurotoxins Affecting Neuroexocytosis
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SV2 Is the Protein Receptor for Botulinum Neurotoxin A
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The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves
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Cited by
Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology
Pirazzini, M., Rossetto, O., Eleopra, R., & Montecucco, C. (2017) · Pharmacological Reviews · doi:10.1124/pr.116.012658 · Cited by 768
Self-citationFacing depression with botulinum toxin: A randomized controlled trial
Wollmer, M. A., de Boer, C., Kalak, N., Beck, J., Götz, T., Schmidt, T., Hodzic, M., Bayer, U., Kollmann, T., Kollewe, K., et al. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.01.027 · Cited by 278
Treatment for spasmodic dysphonia: limitations of current approaches
Ludlow, C. L. (2009) · Current Opinion in Otolaryngology & Head and Neck Surgery · doi:10.1097/moo.0b013e32832aef6f · Cited by 84
Subcutaneous Botulinum Toxin for Chronic Post‐Thoracotomy Pain
Fabregat, G., Asensio‐Samper, J. M., Palmisani, S., Villanueva‐Pérez, V. L., & De Andrés, J. (2013) · Pain Practice · doi:10.1111/j.1533-2500.2012.00569.x · Cited by 35
Joensuu, M., Syed, P., Saber, S. H., Lanoue, V., Wallis, T. P., Rae, J., Blum, A., Gormal, R. S., Small, C., Sanders, S., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022112095 · Cited by 34
Metadata
- Authors
- Antonucci, F., Rossi, C., Gianfranceschi, L., Rossetto, O., & Caleo, M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-04-02
- Volume
- 28
- Issue
- 14
- Pages
- 3689-3696
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2066248618
- Cited by
- 450
- References
- 30
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
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