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Scientists solve the mystery of how Botox attacks nerves and eliminates wrinkles

Every year, millions of people try to look younger by taking injections of Botox, a prescription drug that gets rid of facial wrinkles by temporarily paralyzing muscles in the forehead. Although best known as a cosmetic procedure, Botox injections also have been approved by the Food and Drug Administration (FDA) to treat uncontrolled blinking (blepharospasm), lazy eye (strabismus), involuntary muscle contractions in the neck (cervical dystonia) and acute underarm sweating (severe primary axillary hyperhidrosis).

Botox users might be surprised to learn that they're actually receiving minute injections of a bacterial neurotoxin called botulinum, one of the most poisonous substances known. Exposure to large amounts of botulinum bacteria can cause a paralytic, sometimes-fatal disease called botulism. Last month, several Floridians were hospitalized with botulism after receiving injections of an anti-wrinkle treatment that authorities suspect was a cheap, non-FDA-approved imitation of Botox.

The botulinum toxin works by invading nerve cells, where it releases an enzyme that prevents muscle contraction. In recent years, scientists have determined that the enzyme binds to specific sites on proteins called SNAREs, which form a complex in the synapse between nerve and muscle cells. Without SNAREs, nerves cannot release the chemical signals that tell muscle cells to contract, and paralysis results.

"The botulinum enzyme selectively attacks one of the SNARE proteins and cuts it into two pieces," said Stanford University Professor Axel T. Brunger. "That's sufficient to disrupt its function. But the means by which the enzyme identifies and cleaves its target SNARE has been a subject of much speculation."

Now, Brunger and Stanford graduate student Mark A. Breidenbach have solved part of the puzzle. Their results, which will be published in the Dec. 12 online edition of the journal Nature, could help researchers develop alternative treatments for b
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Contact: Mark Shwartz
mshwartz@stanford.edu
650-723-9296
Stanford University
12-Dec-2004


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