Linked Life Data

22069712

Source:http://linkedlifedata.com/resource/pubmed/id/22069712

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-11-9
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:status
PubMed-not-MEDLINE
pubmed:month
Apr
pubmed:issn
2072-6651
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-55
pubmed:dateRevised
2011-11-14
pubmed:year
2011
pubmed:articleTitle
Re-Assembled Botulinum Neurotoxin Inhibits CNS Functions without Systemic Toxicity.
pubmed:affiliation
Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Email: eferrari@mrc-lmb.cam.ac.uk (E.F.); emaywood@mrc-lmb.cam.ac.uk (E.S.M.); mha@mrc-lmb.cam.ac.uk (M.H.H.); niranjan@mrc-lmb.cam.ac.uk (D.N.).
pubmed:publicationType
Journal Article