Abstract
Botulinum neurotoxin (BoNT) is the most poisonous poison known to mankind for which currently no antidote is available to rescue poisoned nerves. An effective medical countermeasure strategy will be required and would include its efficient delivery specifically to presynaptic nerve terminals. Here we present the report of rescue of botulinum poisoned nerve cells by Mastoparan‐7, a peptide constituent of bee venom that was delivered through a drug delivery vehicle (DDV) constructed from the non‐toxic fragment of botulinum neurotoxin itself. We found that mastoparan‐7 that was delivered into spinal cord cells rescued BoNT/A poisoned cells by restoring over 40% neurotransmitter release. The rescue of the cell poisoning does not seem to occur from inhibition of the endopeptidase activity of BoNT/A against its well known substrate, SNAP‐25, mechanistically involved in the exocytosis process. Rather, Mastoparan‐7 induces a physiological host response apparently unrelated to SNAP‐25 but linked to the phospholipase signal transduction pathway. Our results open new avenues to examine mechanism of exocytosis process, and also to examine alternative cellular mechanism of botulinum neurotoxin action. Successful demonstration of BoNT‐based DDV opens door for its utility for drug delivery against many neuronal and neuron‐muscular disorders.This work was supported JSTO‐CBD/DTRA #3.10003_05_WR_B
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