Why Botulinum Toxin is so Deadly?
Botulinum toxin (Botox) is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species.
It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research. There are seven types of botulinum toxin, named type A–G. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals. Botulinum toxin types A and B are used in medicine to treat various muscle spasms and diseases characterized by overactive muscle. Commercial forms are marketed under the brand names Botox (onabotulinumtoxinA, Allergan), Dysport/Azzalure (abobotulinumtoxinA, Ipsen/Galderma), Xeomin/Bocouture (incobotulinumtoxinA, Merz), and Jeuveau (prabotulinumtoxinA, Evolus/Daewoong).
New research from the University of Wisconsin School of Medicine and Public Health (SMPH) and Scripps Research Institute shows how the astonishingly powerful botulinum toxin uses a similar strategy to latch onto nerve cells, the first step in inactivating them.
The research helps explain how the toxin first attaches to a receptor on the surface of a nerve cell, then looks for a second type of receptor that is nearby. Once the toxin links to this second receptor, it can enter the nerve cell and break a protein needed to deliver molecules that can signal other nerve cells. By blocking this signaling molecule, tiny amounts of botulinum toxin can cause paralysis and even death through respiratory failure. The bacteria that makes this toxin grows in soil, and can be found inside cans of food that were improperly processed. Botulinum toxin is the reason for the extreme danger from bulging cans of food.
Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to nerves which use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis. As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin which triggers it to push across the vesicle membrane and into the cell cytoplasm. Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles can't bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to paralysis.
Journal of Bioterrorism & Biodefence,