Clostridial Neurotoxins: Mechanism of Action of Tetanus and Botulinum Neurotoxins

Tetanus and botulinum neurotoxins are the most potent toxins known as few nanograms are sufficient to kill most mammals. Their exceptional toxicity derives from: a) the absolute specificity for the nervous tissue, whose complete functionality is essential for survival, particularly in the wilderness, and b) their enzymatic activity in the cytosol of nerve terminals where they cleave one after the other all the copies of the core proteins of the neuroexocytosis apparatus causing a persistent blockade of neurotransmitter release. The seven botulinum neurotoxins cause the flaccid paralysis of botulism by acting on peripheric cholinergic nerve terminals. At variance, tetanus neurotoxins enters inside the axon terminals of motoneurons and moves retroaxonally to the spinal cord where it impairs inhibitory interneurons causing the spastic paralysis of tetanus. Because of their specificity of action botulinum neurotoxins are increasingly used in the therapy of diseases caused by hyperfunction of cholinergic nerve terminals and to correct defects due to muscle hyperactivity.