Botulism

Botulism was described much later than tetanus (Kerner 1817 Midura and Arnon 1976 Pickett et al. 1976), and this delayed recognition is due to its much less evident symptoms, which include a generalized muscular weakness with diplopia, ptosis, dysphagia, facial paralysis, and reduced salivation and lacrimation. The paralysis then progressively descends to affect the muscles of the trunk, including respiratory and visceral muscles. All the symptoms of botulism can be ascribed to the blockade of...

Structural Organization of Tetanus and Botulinum Neurotoxins

The similar effect of the eight clostridial neurotoxins (CNTs) on nerve terminals is the result of a closely related protein structure. They are synthesized in the bacterial cytosol as a 150 kDa polypeptide chain without a leader sequence, and are released in the culture medium only after bacterial autolysis. No protein is associated with TeNT, whereas the BoNTs are released as multimeric complexes with a variable set of nontoxic proteins encoded by genes present in the neurotoxin locus (Inoue...

References

Accardi A, Kolmakova-Partensky L, Williams C, Miller C (2004) Ionic currents mediated by a prokaryotic homologue of CLC Cl-channels. J Gen Physiol 123 109-19. Adamson CR, Emley TE, Herbig LJ, Near JA (1997) Effects of nerve growth factor on dihydrote-trabenazine binding to PC12 cells. Neurochem Int 30 411-15. Alfonso A, Grundahl K, Duerr JS, Han HP, Rand JB (1993) The Caenorhabditis elegans unc-17 gene a putative vesicular acetylcholine transporter. Science 261 617-19. Anderson DC, King SC,...

Therapeutic Uses

The demonstration that the inhibition of the nerve-muscle impulse is followed by a functional recovery of the NMJ provides the scientific basis of the rapidly growing use of BoNTs in the therapy of a variety of human diseases caused by hyperfunc-tion of cholinergic terminals and other neurodiseases (Jankovic 2006 Montecucco et al. 1996 Scott et al. 1989 Truong and Jost 2006). Injections of minute amounts of BoNT into the muscle(s) to be paralyzed lead to a depression of the symptoms lasting...

The Mode of Action of Clostridial Neurotoxins

Gangliosides Peripheral Nerves

The structural organization of CNTs is functionally related to the fact that they intoxicate neurons via a four-step mechanism consisting of (1) binding, (2) internalization, (3) membrane translocation, and (4) enzymatic target modification (Figure 4) (Montecucco et al. 1994 Montecucco and Schiavo 1995 Rossetto et al. 2006). The LC is responsible for the intracellular catalytic activity, the amino-terminal 50kDa domain of the H chain (HN) is implicated in membrane translocation, and the...