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.
Written by leading experts in the field botulinum neurotoxins
Provides the current status of basic botulinum neurotoxin research
Provides in depth articles on neurotoxins for further medical applications by means of recombinant technologies
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.
Preface.- Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. - Assembly and function of the Botulinum neurotoxin progenitor complex.- Uptake of botulinum neurotoxin in the intestine.- Double receptor anchorage of botulinum neurotoxins accounts for their exquisite neurospecificity.- The elusive compass of clostridial neurotoxins: deciding when and where to go?.- Synchronized chaperone function of botulinum neurotoxin domains mediates light chain translocation into neurons.- Clostridial neurotoxins light chains:devices for SNARE cleavage mediated blockade of neurotransmission.-Synaptic vesicle proteins – targets and routes for botulinum neurotoxins.- Persistence of Botulinum neurotoxin inactivation of nerve function.- Structure based drug discovery for Botulinum neurotoxins.- Complexity of botulinum neurotoxins: challenges for detection technology.- Progress in cell based assays for Botulinum neurotoxin detection.- Transforming the domain structure of botulinum neurotoxins into novel therapeutics.- Botulinum toxin: application, safety and limitations.- Subject index