MECHANISM OF ACTION OF BOTULINUM NEUROTOXIN

Project: Research project

Project Details

Description

DESCRIPTION (from applicant's abstract): While botulinum neurotoxin (BTx)
is the most poisonous biological toxin identified so far, it has proven to
be a useful therapeutic agent for the treatment of various focal dystonias.
Recently, the mechanism by which BTx inhibits neurotransmitter release was
shown to be by its proteolytic action on a protein needed for the "docking"
of synaptic vesicles. There are however, many unanswered fundamental
questions about the mechanism of action of BTx. The overall objective of
this proposal is to further define its adherence to cells and its in vivo
effect on its synaptosomal protein substrate. This will be accomplished by
determining 1) the number and identity of clustered
ganglioside-oligosaccharide residues needed for its optimum adherence, 2)
the precise region of the carboxy-terminal half of the heavy chain needed
for its adherence to gangliosides, 3) whether the ganglioside binding site
is the only site needed for its cell adherence, and 4) the half-life of BTxA
and BTxE in vivo, as well as their effect on the level of SNAP-25 protein
(SNAP-25 is the docking component acted upon by these two serotypes of BTx).
Answers to these questions may explain the long-lasting effects induced by
BTx, result in its more effective clinical use, and suggest a possible
alternative to the use of antiserum for the treatment of individuals that
come into contact with Clostridium botulinum or its neurotoxin.
StatusFinished
Effective start/end date9/1/967/31/00

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

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