Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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 botulism and perhaps find new medical applications for Botox and other neurotoxins.

Clever machinery

There are seven forms of botulinum neurotoxin produced by seven different strains of the Clostridium botulinum bacterium, explained Brunger, a Howard Hughes Medical Institute investigator who holds professorships in three Stanford departments-molecular and cellular physiology, neurology and neurological sciences, and the Stanford Synchrotron Radiation Laboratory (SSRL). "The seven botulinum neurotoxins cut SNARE proteins at different sites along the surface," he said. "Why that is, we really don’t know exactly."

For the Nature study, the researchers focused on one of the seven forms, botulinum serotype A, which is the active ingredient in Botox. Breidenbach, lead author of the study, spent months in Brunger’s lab trying to crystallize a SNARE/botulinum A complex for laboratory analysis. Unfortunately, the botulinum A samples usually ended up slicing the SNARE target in two, rendering it useless. "The trick that Mark found was to introduce two specific mutations in the botulinum enzyme that would inhibit its function, but not to the degree that it would affect its structure," Brunger said. "These two mutations prevented it from cutting, so we could observe how it interacted with an intact SNARE."

The SNARE/botulinum A crystals were then taken to SSRL and the Lawrence Berkeley National Laboratories, where their structures were determined using a technique called x-ray crystallography. The results, published in Nature, reveal a complicated, three-dimensional maze of twisted proteins that look like gift-wrapping ribbons gone awry. "What we’ve shown is that part of the targeted SNARE protein literally wraps itself around the botulinum A enzyme, using a large portion of the enzyme’s surface for specific interactions," Brunger noted. "That’s the novel finding in our study."

It turned out that the SNARE protein was actually bound to more than two-dozen sites on the enzyme. "Such an extensive interface between a neurotoxin and its target is unheard of," Brunger said. "What botulinum A has accomplished with this large interaction area is a high degree of specificity with just a single unit. Often in biology such specificity is accomplished by having large complexes of auxiliary proteins working together, but these bacteria use a very simple mechanism-in this case, a single protein. It’s an extremely clever machinery."

New applications

Brunger hopes to determine the structures of other botulinum enzymes, along with a closely related neurotoxin that causes tetanus, another serious muscular disorder that affects hundreds of thousands of people worldwide every year. "Perhaps one could develop drugs that would treat botulism and tetanus by competing with specific binding sites on the surface of the neurotoxin,’’ he said. ’’The idea is that you could inject people with a compound that would have an immediate effect."

Further research also could open the door to novel medical applications, Brunger added. For example, recent experiments have shown that Botox may be useful for treating ringing in the ears (tinnitus), urinary incontinence and excess scarring that occurs when a wound heals. "This whole field is very young and evolving, and the picture we have so far is incomplete," he concluded.

Mark Shwartz | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>