Neurotoxicity snake venom

The acidic and basic subunit types presynaptic toxins are fairly common in neurotoxic snake venoms. For instance, such toxins have been isolated from the venoms of C. viridis concolor (Aird et al., 1989b) and C. durissus collilineatus (Lennon and Kaiser, 1990). The... 

Since predators of snakes (and humans) have to deal with snake venoms as defenses, they are included here, even though they serve in predation. Snake venoms are primarily enzymes (proteins), especially of the phospholipase A2 type, which breaks down cell membrane phospholipids hydrolytically. Other snake venoms such as cobrotoxin contain peptides with 60-70 amino acid residues. Pharmacologically, they have neurotoxic, cytotoxic, anticoagulant, and other effects. The neurotoxins, in turn, can have pre- or postsynaptic effects. Snake venoms with both neurotoxic and hemolytic effects on the heart are known as cardiotoxins. Cytotoxins attach to the cells of blood vessels and cause hemorrhage. Snake venom factors may stimulate or inhibit blood clotting. Finally, platelet-active factors can contribute to hemorrhage. 

Snake venoms have been studied extensively their effects are due, in general, to toxins that are peptides with 60 to 70 amino acids. These toxins are cardiotoxic or neurotoxic, and their effects are usually accentuated by the phospholipases, peptidases, proteases, and other enzymes present in venoms. These enzymes may affect the bloodclotting mechanisms and damage blood vessels. Snake bites are responsible for less than 10 deaths per year in the United States but many thousand worldwide. 

Envenomation from a coral snake exerts minimal local pain, and appears as rows of teeth marks. Victims may report that the snake was chewing on the bite site and had to be forcibly removed. Coral snake venom is composed of peptides and enzymes that have not all been identified, but which exert neurotoxicity rather than cytotoxicity. 

Snake venoms are complex mixtures of several different components or fractions that can vary considerably within Crotalinae members. A complete review of venom components is beyond the scope of this review. Depending on the content of the venom, multiple organ systems may be affected. Historically, Crotalinae venom was classified as neurotoxic, hemotoxic, cardiotoxic, or myotoxic, depending on the species of snake involved in the envenomation. This oversimplifies the complex nature of Crotalinae venom. Clinically, a patient may develop such multisystem disorders as platelet destruction, internal bleeding, hypotension, paresthesias, and rhabdomyolysis. 

Elapidae venom is composed of different components that vary among species. The venom of North American species contains fractions that are primarily neurotoxic. The venom results in a bulbar-type cranial nerve paralysis. In contrast to Crotalinae species, venom from North American elapids lacks most of the enzymes and spreading factors that cause local tissue destruction. Elapids from countries other than the United States can contain venom components different than that of North American coral snakes. 

A modified version of the Computer Automated Structure Evaluation (CASE) program has been successfully applied to the study of the neurotoxic and cytotoxic activity of the snake venom toxins. The program identified the sites that seem to be the most relevant to the activity of these two classes of peptides. The knowledge of the three dimensional structure of these peptides together with the relevant fragments selected by the CASE program helped to clarify the differences between the activity of each type of toxin. 

I. Mechanism of toxicity. Snake venoms are complex mixtures of 50 or more components that function to immobilize, kill, and predigest prey. In human victims, these substances produce local digestive effects on tissues as well as hemotoxic, neurotoxic, and other systemic effects. The relative predominance of digestive, hemotoxic, or neurotoxic venom components depends on the species of the snake and geographic variables. 

Crotoxin. Main component of the snake venoms of rattlesnakes (Crotalinae). It is a complex of a basic phospholipase A2 (C. B, Mr 13 500) with an acidic protein (C. A, Mr 10000) which transports the phospholipase to its site of action, the presynaptic membrane of the neuromuscular end-plates. Poisoning leads to local pain and necrosis. Systemic sequelae are tiredness, collapse, and shock through to death. In addition to the neurotoxicity, C. also has hemolytic action. 

Scorpion venoms secretions of the scorpion stinging apparatus. Active principles of S.v. are the neurotoxic scorpamines, which are similar to cobra toxins (see Snake venoms) with respect to M, (6,800-7,200, 4 disulfide bridges, 63-64 amino acid residues of known sequence), amino acid composition (high contents of basic and aromatic amino acids) and activity (both peripheral and central nervous system). The toxin from the North African scorpion, Androc-tonus australia, is one of the most potent known nerve poisons. 

Snake venom is modified saliva that is stored in a specialized structure and has been augmented with a series of toxic proteins. Despite the wide array of proteins that may contribute to the toxicity of snake venom (no fewer than twenty-five), the impacts of venom fall loosely into two categories venoms that impair the circulation of blood, and venoms that impair the electrical connections between locomotor nerves and muscles. The pit vipers of the Americas—the ratdesnakes, for example—generally employ venoms that target circulation, while the kraits of Asia and the mambas of Africa employ neurotoxic venom. 

Insecticides such as DDT elicit their lethal efiects on insects in much the same way as do naturally occurring neurotoxic venoms or poisons that is, the molecule attacks the nervous system. As discussed previously, the proteins embedded in the cell membrane of a neuron that transport sodium, potassium, and calcium are crucial to its overall function. Chemical agents such as snake venom and animal poisons, as well as insecticides, all either stimulate or block the activity of these proteins, interrupting cell-to-cell communication and ultimately causing death. 

Jeng, T. W., Hendon, R. A., and Fraenkel-Conrat, H. (1978). Search for the relationship among the hemolytic, phospholipolytic and neurotoxic activities of snake venoms. Proc. Natl. Acad. Sci. USA 75 600-604. 

To date, more than 120 toxins with neurotoxic activity have been isolated in pure state from elapid and hydrophid (sea-snake) venoms. Over 100 highly homologous postsynaptic neurotoxins belonging to two distinct size groups, short and long neurotoxins, have been sequenced (Yang, 1974,1984 Mebs, 1988 Endo and Tamiya, 1991). Short neurotoxins contain 60-62 amino acid residues with four disulfide bonds, and long neurotoxins comprise... 

Turning now to chemical attack, many predators immobilize their prey by injecting toxins, often neurotoxins, into them. Examples include venomous snakes, spiders, and scorpions. Some spider toxins (Quick and Usherwood 1990 Figure 1.3) are neurotoxic through antagonistic action upon glutamate receptors. The venom of some scorpions contains polypeptide neurotoxins that bind to the sodium channel. 

While most investigations show that sea snake neurotoxins are postsynaptic type, Gawade and Gaitonde (23) stated that Enhydrina schistosa major toxin has dual actions or postsynaptic as well as presynaptic toxicity. E, schistosa venom phospholipase A is both neurotoxic and myotoxic. Neurotoxic action of the enzyme is weak so that there is sufficient time for myonecrotic action to take place (24), Sea snake, L. semifasciata toxin also inhibits transmission in autonomic ganglia, but has no effect on transmission in choroid neurons. 

Neurotoxic venoms of cobras, mambas, and coral snakes Inhibit the enzyme acetylcholinesterase. - This hydrolase normally breaks down the neurotransmitter acetylcholine within nerve synapses. 

The clinical features depend upon the type of snake bite. There are three main patterns neurotoxic, as with elapidae such as cobras and kraits vasculotoxic with alteration in blood coagulation as with vipers and myotoxic as with sea snakes although they are all often complicated by local tissue damage. The severity of poisoning will depend on the amount and potency of venom injected and the patient s general health. 

Bacteria, protozoa, and venomous animals synthesize numerous toxins that are used to kill their prey or to defend themselves. Sea anemones, jellyfish, cone snails, insects, spiders, scorpions, and snakes all make potent and highly specific neurotoxins. Plants form a host of alkaloids and other specialized products, some of which are specifically neurotoxic and able to deter predators. More than 500 species of marine cone snails of the genus Conus synthesize a vast array of polypeptide toxins (conotoxins), 487-489 some with unusual posttranslational modifications.490 491 The slow-moving snails are voracious predators that use their toxins, which they inject with a disposible harpoonlike tooth,492 to paralyze fish, molluscs, or worms.493... 

The venom of the mamba snake (Dendroaspis angusticeps, Dendroaspis polylepis, Dendroaspis viridis, Dendroaspis jamesoni) contains a mixture of neurotoxic compounds, including postsynaptic cholinoreceptor a-neurotoxins, dendrotoxins, fasciculins, and muscarinic toxins (Hawgood and Bon, 1991). Effects at the NMJ include AChE inhibition by fasciculins and increased presynaptic release of ACh by dendrotoxins (polypeptides that facilitate ACh release in response to nerve stimulation) together with the high ACh content of mamba toxin (6-24 mg/g), these effects are synergistic and enhance neurotoxicity and lethality. Moreover, the venom may contain other components that have a synergistic action with dendrotoxin. 

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