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Primary cultures of embryonic chicken neurons for sensitive cell-based assay of botulinum neurotoxin: Implications for therapeutic discovery

  1. Author:
    Stahl, A. M.
    Ruthel, G.
    Torres-Melendez, E.
    Kenny, T. A.
    Panchal, R. G.
    Bavari, S.

  2. Author Address

    USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21701 USA.;Ruthel, G, USA, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA.;gordon.ruthel@amedd.army.mil sina.bavari@amedd.army.mil
    1. Year: 2007
    2. Date: Apr
  2. Journal: Journal of Biomolecular Screening
    1. 12
    2. 3
    3. Pages: 370-377
  4. Type of Article: Article
  5. ISSN: 1087-0571
  1. Abstract:

    Botulinum toxin is an exceedingly potent inhibitor of neurotransmission across the neuromuscular junction, causing flaccid paralysis and death. The potential for misuse of this deadly poison as a bioweapon has added a greater urgency to the search for effective therapeutics. The development of sensitive and efficient cell-based assays for the evaluation of toxin antagonists is crucial to the rapid and successful identification of therapeutic compounds. The authors evaluated the sensitivity of primary cultures from 4 distinct regions of the embryonic chick nervous system to botulinum neurotoxin A (BoNT/A) cleavage of synaptosomal-associated protein of 25 kD (SNAP-25). Although differences in sensitivity were apparent, SNAP-25 cleavage was detectable in neuronal cells from each of the 4 regions within 3 It at BoNT/A concentrations of 1 nM or lower. Co-incubation of chick neurons with BoNT/A and toxin-neutralizing antibodies inhibited SNAP-25 cleavage, demonstrating the utility of these cultures for the assay of BoNT/A antagonists.

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External Sources

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  2. DOI: 10.1177/1087057106299163
  3. View record in Web of Science®
  4. WOS: 000245753000008

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