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Physiological Reviews, Vol. 80, No. 2, April 2000, pp. 717-766
Copyright ©2000 by the American Physiological Society
Imperial Cancer Research Fund, London, United Kingdom; Centro Consiglio Nazionale delle Ricerca di Farmacologia Molecolare e Cellulare e Centro "B. Ceccarelli," Dipartimento di Farmacologia, Università di Milano, Milan; and Centro Consiglio Nazionale delle Ricerca Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, Padua, Italy
Schiavo, Giampietro,
Michela Matteoli, and
Cesare Montecucco.
Neurotoxins Affecting Neuroexocytosis. Physiol. Rev. 80: 717-766, 2000.
Nerve terminals are specific sites of action of a very
large number of toxins produced by many different organisms. The
mechanism of action of three groups of presynaptic neurotoxins that
interfere directly with the process of neurotransmitter release is
reviewed, whereas presynaptic neurotoxins acting on ion channels are
not dealt with here. These neurotoxins can be grouped in three large families: 1) the clostridial neurotoxins that act inside
nerves and block neurotransmitter release via their metalloproteolytic activity directed specifically on SNARE proteins; 2) the
snake presynaptic neurotoxins with phospholipase A2
activity, whose site of action is still undefined and which induce the
release of acethylcholine followed by impairment of synaptic functions; and 3) the excitatory latrotoxin-like neurotoxins that
induce a massive release of neurotransmitter at peripheral and central synapses. Their modes of binding, sites of action, and biochemical activities are discussed in relation to the symptoms of the diseases they cause. The use of these toxins in cell biology and neuroscience is
considered as well as the therapeutic utilization of the botulinum neurotoxins in human diseases characterized by hyperfunction of cholinergic terminals.
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