Botulin toxin
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Template:WMD/Chemical Botulin toxin or botox is the toxic compound produced by the bacterium Clostridium botulinum. It is a protease that breaks down one of the fusion proteins (docking proteins that anchor the vesicle to the membrane) that allow neurons to release acetylcholine at a neuromuscular junction. By inhibiting acetylcholine release, the toxin interferes with nerve impulses and causes paralysis of muscles in botulism. The toxin is a two-chain polypeptide with a 100 kDa heavy chain joined by a disulphide bond to a 50-kD light chain. It is possibly the most toxic substance known, with a lethal dose of about 300 pg/kg, meaning that somewhat over a hundred grams could kill every human living on the earth.
Botulin toxin is used (usually under a trademarked name such as "Botox") for producing long-term (months) paralysis of muscles. This was intended for the relief of uncontrollable muscle spasms, but is increasingly being used for cosmetic purposes, to paralyse facial muscles as a means of concealing wrinkles.
Botulin toxin has always been considered an ideal agent for biological warfare (though the distinction from chemical warfare is a thin one), since it oxidises rapidly on exposure to air, so an area attacked with a toxin aerosol would be safe to enter within a day or so. There are no documented cases of the toxin actually being used in warfare. There has been concern over the use of botulin toxin as a terrorist weapon, but it appears to not be ideal for this purpose. The vials of toxin used therapeutically are considered impractical for use by terrorists because each vial has only an extremely small fraction of the lethal dose for humans. Another reason the toxin is considered impractical is that the bacterium in question is anaerobic (cannot survive in the presence of oxygen). This would make it extremely difficult for terrorists to produce enough of the toxin to launch a significant attack.
The toxin's properties did not escape the attention of the Aum Supreme Truth cult in Japan, who actually set up a plant for bulk production of this agent, though their terrorist and assassination attacks used the nerve agent sarin instead, it being easier to disperse and faster acting.
The CIA once prepared some cigars of Fidel Castro's favorite brand which had been saturated with botulinum toxin, for the possibility of an assassination attempt. The cigars were never used, but when tested years later were still found to be effective. See [1] (http://www.parascope.com/mx/articles/castroreport.htm).
Medical uses
Botox is used to relieve the symptoms of dystonia. With the assistance of an EMG, the physician (susually a neurologist) injects very small doses of botox into the area that controls the muscles which the dystonia patient has difficulty moving.
Botox is also used as a treatment against hyperhidrosis (excessive sweating).
Chemical mechanism of toxicity
The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to leave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein. The SNAP-25 protein is required for the release of neurotransmitter from the axon endings [2] (http://www.jbc.org/cgi/content/full/278/2/1363).
External links
- Mimetrek Systems: Toxins (http://www.mitretek.org/home.nsf/HomelandSecurity/Toxins#botulinum)
- FDA: A Poison that can Heal (http://www.fda.gov/fdac/features/095_bot.html)
- Botox Fact Sheet (http://www.fact-sheets.com/health/drugs-medications/botox/)
- Botox the cosmetic (http://www.plasticsurgery.com/botox_injections/default.htm)
- botox Infos (http://www.1-botox.com)de:Botulinumtoxin