Paralysis botulinum neurotoxins

Botulinum neurotoxins are widely used as therapeutic agents to cause reduction or paralysis of skeletal muscle contraction. They are used to treat cervical dystonia, which causes regional involuntary muscle spasms often associated with pain. Moreover, they are used in strabism, blepharospasm, hemifacial spasm, and... 

The role of C2 toxin in disease is not clear because all C. botulinum strains that produce C2 toxin also synthesize extremely potent neurotoxins, the effector molecules of botulism. When Simpson compared the pharmacological properties of C. botulinum neurotoxin type Cl with C2 toxin in detail, it became obvious that C2 toxin does not cause the flaccid paralysis symptoms attributed to classic botulism. However, isolated C2 toxin is a potent enterotoxin that proves lethal in various animals 2 pmol of C2 toxin readily kill mice, rats, guinea pigs, and chickens within 1 h after application. For mice, the LD50 (i.v.) of C2 toxin is less than 50 ftnol. Ohishi and Odagiri also reported that C2 toxin causes necrotic, hemorrhagic lesions in the intestinal wall, whereas Simpson reported that C2 toxin elicits hypotension as well as fluid accumulation in the lungs. ... 

Tetanus toxin poisoning produces tetanus, i.e. muscle contractions resulting in spastic paralysis. In contrast, Botulinum neurotoxins cause botulism, which is characterized by flaccid paralysis. This difference reflects differences in the anatomical level of action of these toxins. TeTx acts primarily on the CNS where it blocks exocytosis from inhibitory glycinergic synapses in the spinal cord. Loss of inhibitory control results in motoneuron firing. BoNTs act primarily in the periphery where they inhibit acetylcholine release at the neuromuscular junctions. 

Jurasinski, C.V., Lieth, E., Dang Do, A.N., and Schengrund, C.L. 2001. Correlation of cleavage of SNAP-25 with muscle function in a rat model of botulinum neurotoxin type A induced paralysis. Toxicon 39 1309-1315. 

Lundh, H., Leander, S., and Thesleff, S. 1977. Antagonism of the paralysis produced by botulinum toxin in the rat. The effects of tetraethylammonium, guanidine and 4-aminopyridine. J. Neurol. Sci. 32 29 3. MacKenzie, L, Bumstock, G., and Dolly, J.O. 1982. The effects of purified botulinum neurotoxin type A on... 

The seven serotypes of botulinum toxin produced by Clostridium botulinum are the most toxic substances known. They are associated with lethal food poisoning after the consumption of canned foods. This family of toxins was evaluated by the United States as a potential biological weapon in the 1960s and is believed to be an agent that could be used against our troops. Unlike other threat toxins, botulinum neurotoxin appears to cause the same disease after inhalation, oral ingestion, or injection. Death results from skeletal muscle paralysis and resultant ventilatory failure. Because of its extreme toxicity, the toxin typically cannot be identified in body fluids, other than nasal... 

Botulism, the deadly food poisoning disease is caused by the growth of various strains of Clostridium botulinum in food. The organism produces a large polypeptide (neurotoxin) which is the most toxic protein known to the human kind. Seven serotypes of botulinum neurotoxins produced by different strains of C. botulinum have been characterized, and serotypes A, B and E are known to cause botulism in humans. Ingestion of food contaminated with the neurotoxin causes flaccid muscle paralysis that can result in patients death. Wound botulism has also been reported where the organism can grow in the wounds, and produces the neurotoxin that causes paralysis. 

Botulinum neurotoxins, produced by the anaerobic bacterium Clostridium bo-tulinum, are the most toxic poisons known to man. The neurotoxins are food poisons. Once ingested, the neurotoxin is absorbed through the intestinal mucosal layer into the blood stream. It acts at the neuromuscular junction to inhibit the release of acetylcholine (a neurotransmitter) from nerve endings (Simpson, 1989). The result is the dreaded botulism disease, which is manifested by flaccid muscle paralysis. 

Delayed-action paralytic neurotoxins that block the release of acetylcholine causing a symmetric, descending flaccid paralysis of motor and autonomic nerves. Paralysis always begins with the cranial nerves. Toxins are obtained from an anaerobic bacteria (Clostridium botulinum). Toxin A is a white powder or crystalline solid that is readily soluble in water. It is stable for up to 7 days as an aqueous solution. All toxins are destroyed by heat and decompose when exposed to air for more than 12 h. 

Hughes R, Whaler BC (1962) Influence of nerve-ending activity and of drugs on the rate of paralysis of rat diaphragm preparations by cl. botulinum type a toxin. J Physiol 160 221-33 Humeau Y, Doussau F, Grant NJ, Poulain B (2000) How botulinum and tetanus neurotoxins block neurotransmitter release. Biochimie 82 427 16... 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

Several toxic proteins act as neurotoxins by disrupting the activity of synapses. (A synapse is a junction between two neurons or between a neuron and a muscle cell.) The pain, tremors, and irritability that result from black widow spider bites are caused by a-latrotoxin (125,000 D). This molecule, a single polypeptide, stimulates a massive release of the neurotransmitter acetylcholine (ACh). In contrast, ACh release is inhibited by botulinum toxin, a mixture of several proteins produced by the bacterium Clostridium botulinum. Botulism, a malady most commonly caused by eating contaminated canned food, is characterized by vomiting, dizziness, and sometimes paralysis and death. A related species,... 

---