| Autor: |
Bazbek Davletov, Giampietro Schiavo, Dhevahi Niranjan, Ornella Rossetto, Michael H. Hastings, Marco Pirazzini, Matteo Caleo, Enrico Ferrari, Elizabeth S. Maywood, Laura Restani |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
|
| Zdroj: |
Toxins, Vol 3, Iss 4, Pp 345-355 (2011) |
| Druh dokumentu: |
article |
| ISSN: |
2072-6651 |
| DOI: |
10.3390/toxins3040345 |
| Popis: |
The therapeutic potential of botulinum neurotoxin type A (BoNT/A) has recently been widely recognized. BoNT/A acts to silence synaptic transmission via specific proteolytic cleavage of an essential neuronal protein, SNAP25. The advantages of BoNT/A-mediated synaptic silencing include very long duration, high potency and localized action. However, there is a fear of possible side-effects of BoNT/A due to its diffusible nature which may lead to neuromuscular blockade away from the injection site. We recently developed a “protein-stapling” technology which allows re-assembly of BoNT/A from two separate fragments. This technology allowed, for the first time, safe production of this popular neuronal silencing agent. Here we evaluated the re-assembled toxin in several CNS assays and assessed its systemic effects in an animal model. Our results show that the re-assembled toxin is potent in inhibiting CNS function at 1 nM concentration but surprisingly does not exhibit systemic toxicity after intraperitoneal injection even at 200 ng/kg dose. This shows that the re-assembled toxin represents a uniquely safe tool for neuroscience research and future medical applications. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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