Types of neurotoxins

Before discussing the structure of the neurotoxins, it is necessary to define the types of neurotoxins. Three types of neurotoxins have been found so far in snake venoms. The first one is a postsynaptic neurotoxin, the second is a presynaptic neurotoxin, and the last is a cholinesterase inhibiting neurotoxin. Most sea snake venoms seem to contain only the postsynaptic neurotoxin. Only in Enhydrina... 

Another type of neurotoxin found in sea snake venoms is a hybrid type structurally situated between the short-chain and long-chain types. As can be seen in Table IV, two toxins shown here have a long stretch of segment 4, yet there is no disulfide bond in this portion. 

The similarity of the primary structure of different sea snake venoms has already been discussed. Postsynaptic neurotoxins from Elapidae venom have been extensively studied. Elapidae include well-known snakes such as cobra, krait, mambas, coral snakes, and all Australian snakes. Like sea snake toxins, Elapidae toxins can also be grouped into short-chain (Type I) and long-chain (Type II) toxins. Moreover, two types of neurotoxins are also similar to cardiotoxins, especially in the positions of disulfide bonds. However, amino acid sequences between cardiotoxins and sea snake and Elapidae neurotoxins are quite different. In comparing the sequence of sea snake and Elapidae neurotoxins, there is a considerable conservation in amino acid sequence, but the difference is greater than among the various sea snake toxins. 

In general, sensitivity of a given preparation to clostridial neurotoxins depends on the type of neurotoxin. For instance, BoNT/A is particularly potent in poisoning peripheral cholinergic nerve terminals (i.e. neuromuscular junctions), whereas TeTx is most potent for CNS preparations. However, all eight neurotoxins are able to inhibit exocy-... 

There are several types of neurotoxins and their structures the site of action and the mechanism are not identical. Snake neurotoxins are peripheral neurotoxins, rather than centrally neurotoxic apparently they do not pass through the blood-brain barrier. 

D. Antiacetylcholinesterase Neurotoxins. The fourth type of neurotoxin is the one that binds to acetylcholinesterase (Rodriquez-Ithurralde et al., 1981 Cervenansky et al., 1991). When acetylcholinesterase is not functioning, acetylcholine (after binding to the acetylcholine receptor) cannot be hydrolyzed consequently, normal nerve transmission is impaired. Acetylcholinesterase action of D. angusticeps venom was first reported by Ro-driguez-Ithurralde et al. (1983). 

A striking feature of the toxic compounds considered so far is that many of them are neurotoxic to vertebrates or invertebrates or both. The nervous system of animals appears to be a particularly vulnerable target in chemical warfare. Not altogether surprisingly, all the major types of insecticides that have been commercially successful are also neurotoxins. Indeed, in 2003, neurotoxic insecticides accounted for over 70% of total insecticide sales globally (Nauen 2006). 

There are four disulfide bonds in short-chain (Type I) neurotoxins. This means that there are eight half-cystines. However, all Hydrophiinae toxins have nine halfcystines with one cysteine residue. An extra cysteine residue can be readily detected from the Raman spectrum as the sulfhydryl group shows a distinct S-H stretching vibration at 2578 cm" Some Laticaudinae toxins do not have a free cysteine residue as in the cases of L. laticaudata and L. semifasciata toxins. In long toxins (Type II) there are five disulfide bonds (Table III). 

Giuhan D, Vaca K, Noonan CA (1990) Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science 250(4987) 1593-1596 Giuhan D, Wendt E, Vaca K, Noonan CA (1993) The envelope glycoprotein of human immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes. Proc Natl Acad Sci USA 90(7) 2769-2773... 

Botulism is a potent neurotoxin produced from Clostridium botulinum that is an anaerobic, spore-forming bacterium. There are three different types ofbotulism Foodborne botulism occurs when a person ingests a pre-formed toxin that leads to illness within a few hours or days. Foodborne botulism is a public health emergency because the contaminated food may still be available. Infant botulism occurs in a small number of susceptible infants each year who harbor C. botulinum in their intestinal tract. Wound botulism occurs when wounds are infected with C. botulinum that secretes the toxin. Approximately 100 cases of the three types of botulism are reported within the United States each year about 5 percent are wound botulism, 25 percent are foodborne botulism, and a full 70 percent are infant botulism. Death can result from respiratory failure, but those who survive may have fatigue and shortness of breath for years. 

M toxin (12S) consists of neurotoxin and non-toxic non-hemaglutynin (NTNH) components. It is produced by all types of C. botulinum, except C. botulinum type G. 

Powder for injection (vacuum-dried) 100 units of vacuum-dried Clostridium botulinum toxin type A neurotoxin complex- (Rx)... 

Ion channels have been purified from several types of excitable cells. The proteins that make up the voltage-gated Na+ channels of brain neurons were first identified by labeling them with reactive derivatives of neurotoxins obtained from scorpions. Intact channels were purified from both brain and muscle after solubilization with detergents. When the purified proteins were incorporated into phospholipid vesicles or planar bilayer membranes, they were found to conduct Na+ across the membrane. The ion specificity of the reconstituted channels and the alterations of the conductance in response to changes in Aift or to various neurotoxins were similar to the properties of the original nerve or muscle membranes. In addition to scorpion toxins, a variety of other specific neurotoxins bind to the purified channels and inhibit their activities. These include tetrodotoxin (a poison obtained from... 

Eleopra R, Tugnoli V, Quatrale R, Gastaldo E, Rossetto O et al. (2002) Botulinum neurotoxin serotypes A and C do not affect motor units survival in humans an electrophysiological study by motor units counting. Clin Neurophysiol 113 1258-64 Eleopra R, Tugnoli V, Quatrale R, Rossetto O, Montecucco C (2004) Different types of botulinum toxin in humans. Mov Disord 19 Suppl 8 S53-9... 

Niemann H (1991) Molecular biology of clostridial neurotoxins. In Alouf J, Freer J (eds) A source-book of bacterial protein toxins. Academic Press, London, pp 303 18 Nishiki T, Tokuyama Y, Kamata Y, Nemoto Y, Yoshida A et al. (1996) The high-affinity binding of Clostridium botulinum type b neurotoxin to synaptotagmin ii associated with gangliosides gtlb/gdla. FEBS Lett 378 253-7... 

Sellin LC, Kauffman JA, Dasgupta BR (1983) Comparison of the effects of botulinum neurotoxin types A and E at the rat neuromuscular junction. Med Biol 61 120-5 Sheridan RE (1998) Gating and permeability of ion channels produced by botulinum toxin types A and E in PC12 cell membranes. Toxicon 36 703-17 Shone CC, Hambleton P, Melling J (1987) A 50-kDa fragment from the NH2-terminus of the heavy subunit of Clostridium botulinum type A neurotoxin forms channels in lipid vesicles. Eur J Biochem 167 175-80... 

The roles of NF-kB in neuronal survival are complex. Mice lacking the p50 subunit of NF-kB exhibit increased neurotoxin-induced damage to neuronal cells as compared to wild-type mice (Yu et al., 1999), but decreased damage following a focal ischemic stroke (Nurmi et al., 2004). It was observed that activation of NF-kB is correlated with neurotoxicity in other paradigms. It is possible that the trophic or toxic dichotomy of NF-kB could be attributed to the specific subunits of the activated complex and the differential regulation in different types of cells. 

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