Botulinum toxin neurotoxicity

Baizabal-CarvaUo JF, Jankovic J, Feld J. Hu-Kke symptoms and associated immunological response following therapy with botulinum toxins. Neurotox Res 2013 24 298-306. 

Paralytic shellfish poison, like botulinum toxin, is a neurotoxic substance and can also affect certain muscles, including the heart, which are under nervous system control. Some poisoned humans who have recovered from the effects of PSP have described the early stages of intoxication as not at all unpleasant a tingling sensation in the lips and face and a feeling of calm. Those who die from PSP ingestion do so because of respiratory failure. 

Eleopra R, Tugnoli V, Quatrale R, Rossetto O, Montecucco C et al. (2006) Clinical use of non-A botulinum toxins botulinum toxin type C and botulinum toxin type F. Neurotox Res 9 127-31 Evans ER, Sutton JM, Gravett A, Shone CC (2005) Analysis of the substrate recognition domain determinants of botulinum type B toxin using phage display. Toxicon 46 446-53... 

Jahn R, Lang T, Siidhof TC (2003) Membrane fusion. Cell 112 519-33 Jankovic J (2006) Botulinum toxin therapy for cervical dystonia. Neurotox Res 9 145-8 Jankovic J, Schwartz K (1995) Response and immunoresistance to botulinum toxin injections. Neurology 45 1743-6... 

Schantz, E.J. and Johnson, E.A. (1992). Properties and use of botulinum toxin and other microbial neurotoxic medicine. Microbiological Reviews 56 80-99. 

The seven types of botulinum toxin " and the tetanus toxin " are the most neurotoxic substances known. Only 10 molecules are sufficient to kill a mouse. Both toxins are zinc proteases, which block presynaptic transmitter release by cleaving specific synaptic vesicles proteins (see p. 1780 and Fig. 

Dressier, D., Eleopra, R. 2006. Clinical use of non-A botulinum toxins botulinum toxin type B, Journal Neurotoxicity Research 9(2—3), 121—125. 

So far eight different botulinum toxins (A, B, Cl, C2, D, E, F, G) have been described which are produced by various strains of Clostridium botulinum (1). Whereas seven of the botulinum toxins are neurotoxins and block the release at the cholinergic synapses, botulinum C2 toxin is not neurotoxic and acts on various non-neuronal tissues (1-3). It has been shown that component I of the binary botulinum C2 toxin possesses ADP-ribosyltransferase activity (4) on the eukaryotic substrate non-muscle actin (5). Here we describe another ADP-ribosyltransferase which is produced by certain strains of Clostridium botulinum type C. In order to distinguish the novel ADP-ribosyltransferase from botulinum neurotoxin Cl and botulinum C2 toxin we termed this enzyme C3. 

Harris JB, Grubb BD, Maltin CA, Dixon R (2000) The neurotoxicity of the venom phospholipases A(2), notexin and taipoxin. Exp Neurol 161 517-26 Haug G, Wilde C, Leemhuis J, Meyer DK, Aktories K et al. (2003) Cellular uptake of Clostridium botulinum C2 toxin membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain. Biochemistry 42 15284-91 Hauschild A (1993) Epidemiology of human foodborne botulism. In Hauschild A, Dodds KL (eds) Clostridium botulinum ecology and control in foods. Marcel Dekker, Inc. New York, pp 69-104... 

Schiavo G, Papini E, Genna G, Montecucco C (1990) An intact interchain disulfide bond is required for the neurotoxicity of tetanus toxin. Infect Immun 58 4136 11 Scott AB, Magoon EH, McNeer KW, Stager DR (1989) Botulinum treatment of strabismus in children. Trans Am Ophthalmol Soc 87 174-180 discussion 180 1 Scott D (1997) Phospholipase A2 structure and catalytic properties. In Kini R (ed) Venom phospholipase A2 enzymes structure, function and mechanism. John Wiley Sons, Chichester, p 97-128. 

Prepare a culture of a C2 toxin-producing strain of C botulinum it is preferable to use strains, that do not produce botulinum neurotoxin, because the neurotoxin interferes the determination of toxicity of C2 toxin. Otherwise, use anti-neurotoxin serum to neutralize the neurotoxic activity. 

The botulinum neurotoxins (BoNTs) comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium Clostridium botulinum and in rare cases by Clostridium baratii and Clostridium butyricum (Habermann and Dreyer, 1986 Harvey et ah, 2002 Simpson, 2004). These toxins act on peripheral cholinergic synapses to inhibit spontaneous and impulse-dependent release of acetylcholine (ACh) (Brooks, 1956 Kao et al., 1976). Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation (Dickson and Shevky, 1923). The BoNTs are the most potent substances in nature, and exposure to as httle as 1-3 ng/kg may be sufficient to cause human lethahty (GUI, 1982 Middlebrook and Franz, 1997 Amon et al., 2001). 

The botulinum neurotoxins (BoNTs) comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium, Clostridium botulinumThese toxins act on peripheral cholinergic... 

Botulism is a serious neuroparalytic illness that affects humans and various domestic and wild animal and avian species. It is due to the neurotoxic effect of a toxin produced by the anaerobic bacterium Clostridium botulinum. Botulism is most commonly known as a foodbome intoxication of humans it also can result from growth of the toxigenic organism in a wound or, in the case of infant botulism, from colonization of the intestinal tract. 

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