Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update

Abstract

Tetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons, metalloproteases specifically cleaving the SNARE proteins that are essential for the release of neurotransmitters. Research on their mechanism of action is intensively carried out in order to devise improved therapies based on antibodies and chemical drugs. Recently, major results have been obtained with human monoclonal antibodies and with single chain antibodies that have allowed one to neutralize the metalloprotease activity of botulinum neurotoxin type A1 inside neurons. In addition, a method has been devised to induce a rapid molecular evolution of the metalloprotease domain of botulinum neurotoxin followed by selection driven to re-target the metalloprotease activity versus novel targets with respect to the SNARE proteins. At the same time, an intense and wide spectrum clinical research on novel therapeutics based on botulinum neurotoxins is carried out, which are also reviewed here.

Comparative analysis of antigenic strength and in vivo serum antibodies concentration of tetanus toxoid vaccine adsorbed in Pakistan

“…Ramon titration method identifies the product's antigen content, and the reaction is called flocculation. The antigen content is expressed either in Lf/ml or Lf/dose ( Pirazzini et al, 2022 ). The toxin neutralization test is a reliable and widely used technique for the measurement of tetanus toxoid.…”

Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

“…Thereby, BoNTs target the motoneuron endings of the peripheral nervous system and block the release of acetylcholine, leading to a flaccid paralysis (botulism). In contrast, TeNT enters the central nervous system via retrograde transport through motoneurons and specifically inhibits the release of neurotransmitters (glycine, gamma aminobutyric acid (GABA)) in inhibitory interneurons, thus disrupting the negative control exerted by inhibitory interneurons over motoneurons, resulting in spastic paralysis (tetanus) [1,2].…”

How Does Botulinum Toxin Inhibit Itch?

“…There are also various off-label uses of BoNT in various medical fields [ 16 , 17 ]. Along the way, efforts by basic scientists have resulted in presenting the molecular structures of botulinum toxins and their mechanisms of action for various clinical conditions [ 18 , 19 , 20 ].…”