Botulinum Neurotoxins

The extremely potent substance botulinum neurotoxin (BoNT) has attracted much interest in diverse fields. Originally identified as cause for the rare but deadly disease botulism, military and terrorist intended to misuse this sophisticated molecule as biological weapon. This caused its classification as select agent category A by the Centers for Diseases Control and Prevention and the listing in the Biological and Toxin Weapons Convention. Later, the civilian use of BoNT as long acting peripheral muscle relaxant has turned this molecule into an indispensable pharmaceutical world wide with annual revenues >$1.5 billion. Also basic scientists value the botulinum neurotoxin as molecular tool for dissecting mechanisms of exocytosis. This book will cover the most recent molecular details of botulinum neurotoxin, its mechanism of action as well as its detection and application.

Botulinum neurotoxins are the most toxic natural substances and represent a major threat to the population when intentionally released in bioterrorist attacks. On the other hand, during the past two decades botulinum neurotoxins have become established as indispensable drugs for the treatment of a variety of severe neurological disorders. The need for efficient countermeasures as well as the expansion into additional fields of therapeutic application, call for comprehensive information on the botulinum neurotoxin molecules and their mode of action. Our knowledge of this subject has made great strides in recent years, setting the stage for the development of new botulinum neurotoxin-based molecules and novel applications.

This book reviews the current status of basic botulinum neurotoxin research. The first part describes the genetic variability of the toxin-producing bacteria, and sheds light on each step from toxin ingestion to the abrogation of synaptic signaling including the intestinal passage and absorption, nerve cell binding and entry, and intracellular substrate cleavage. The remaining chapters detail progress made in detection methods for botulinum neurotoxins, the development of botulinum neurotoxin inhibitors, and strategies to refine the neurotoxins for further medicinal applications by means of recombinant technologies.