Accession Number:

ADA243156

Title:

Novel Treatments for Botulism: Development of Antagonists for Identified Steps in the Action of Botulinum Neurotoxins

Descriptive Note:

Final rept. 18 Jan 88-17 Apr 91

Corporate Author:

IMPERIAL COLL OF SCIENCE AND TECHNOLOGYLONDON (UNITED KINGDOM)

Personal Author(s):

Report Date:

1991-09-20

Pagination or Media Count:

79.0

Abstract:

Using a combination of electrophysiological and biochemical techniques, the action of botulinum neurotoxin BoNT was shown conclusively to involve 1 binding targetting to ecto-acceptors on cholinergic neurons, 2 acceptor-mediated uptake and, 3 block of Ca24-dependent release of transmitters. Domainschains in BoNT responsible for each step were identified. One useful antagonist of the toxins binding was developed, in addition to a monoclonal antibody capable of neutralizing the intracellular poisoning. Insights into the molecular action of BoNT were gained, particularly involvement of microtubules in the base of B and, possible, a large phosphorylated protein concerned with exocytosis. Equivalent experiments on tetanus toxin, and chimeric mixtures of both toxins, yielded valuable information for possible future targetting of agents to cholinergic and non-cholinergic neurons. A more detailed summary is included in the report.

Subject Categories:

  • Biochemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE