Botulinum neurotoxins molecular action

The botulinum neurotoxins and the snake presynaptic PLA2 neurotoxins share three levels of interest (1) they are pathogenic to humans and animals, (2) they contribute to the understanding of the molecular steps of neurotransmission, and (3) their present and future clinical applications. In this chapter, these neurotoxins are considered in terms of mode of action and in relation to their potential use in cell biology and neuroscience research as well as therapeutics in some human neurodisorders. 

Miyake M, Ohishi I (1987) Response of tissue-cultured cynomolgus monkey kidney cells to botulinum C2 toxin. In Microbial Pathogenesis. 3 279-86 Montecucco C, Schiavo G (1994) Mechanism of action of tetanus and botulinum neurotoxins. In Molecular Microbiology. 13 1-8 Muller H, von Eichel-Streiber C, Flabermann E (1992) Morphological changes of cultured endothelial cells after microinjection of toxins that act on the cytoskele-ton. In Infect Immun. 60 3007-10... 

Montecucco C, Schiavo G, Tugnoli V, Degrandis, D (Oct. 1996) Botulinum Neurotoxins Mechanism of action and therapeutic applications. Molecular Medicine Today 2 (10) 418-424... 

Fig. 8. Proposed molecular mechanism of botulinum neurotoxin action.

The mode of action of the botulinum neurotoxin is not well understood at the molecular level. Based on some experimental evidence and analogies with other dichain... 

Nevertheless, the selectivity of action of many of these toxins means they have been harnessed in medical therapeutics (more so in experimental pharmacology and physiology). Toxins that have been, or still are, used in medicine include atropine and hyoscine, botulinum toxin, colchicine, digitalis alkaloids, eserine, morphine, ouabain, picrotoxin, strychnine, veratridine, vinca alkaloids and many more. These work by an action at a defined molecular site, whether ion channel, neurotransmitter receptor, enzyme, carrier molecule (pump) or intracellular organelle. Several of these particular examples have their most obvious effects on neurotransmission, and are dealt with under neurotoxins. 

Guyton, A.C. and MacDonald, M.A. 1947. Physiology of botulinum toxin. Arch. Neurol. Psych. 57 578-592. Habermann, E. and Dreyer, F. 1986. Clostridial neurotoxins handling and action at the cellular and molecular... 

---