[Mechanism of action and therapeutic uses of botulinum and tetanus neurotoxins].
Botulinum neurotoxins are produced by anaerobic spore forming bacteria, Clostridiumbotulinum. They are synthesized as a single chain protein (150kDa) which is not or weakly active. The active form results from proteolysis that cleaves the precursor into a light chain (about 50kDa) and a heavy chain (about 100kDa) which are linked by a disulfide bridge. The heavy chain is involved in the recognition of a specific neurone surface receptor and mediates the internalization of the light chain into the cytosol. The light chain is responsible for the intracellular activity. It catalyzes the proteolysis of SNARE proteins which are involved in the exocytosis of synaptic vesicles containing acetylcholine. Hence, the release of acetylcholine at the neuromuscular junction is blocked leading to a flaccid paralysis. The tetanus neurotoxin shares with botulinum neurotoxins a common structure and mechanism of action. Tetanus neurotoxin blocks the release of neurotransmitters in the inhibitory interneurons leading to spastic paralysis. The paralytic properties of the botulinum neurotoxins are used to treat certain myoclonies such as blepharospasm, torticolis, hemifacial paralysis. Botulinum neurotoxins are thus efficient therapeutic agents helpful in avoiding surgery.
Popoff
M R
MR
Centre National de Référence des Bactéries Anaérobies, Institut Pasteur, 28 rue du Dr. Roux, F. 75724 Paris cedex 15.
Marvaud
J C
JC
Raffestin
S
S
D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001905:Botulinum Toxins / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D013744:Tetanus Toxin / Q000494:pharmacology* / Q000627:therapeutic use*
D018726:Anti-Dyskinesia Agents; D013744:Tetanus Toxin; D001905:Botulinum Toxins