Botox toxin can kill. These researchers just discovered how it enters the brain

Australian researchers have uncovered the specific molecular mechanism for how ‘Botox’ is able to enter neurons in the brain.

Botox is among the world’s most widely used cosmetic procedures, used by millions of people every day. A tiny number of those result in adverse reactions.

Which is not surprising because Botox, better known as botulinum toxin type A, is the most toxic compound known. A perfect illustration of the concept ‘the dose makes the poison’. A few teaspoons of the toxin would be enough to kill millions of people.

The researchers – who published their findings in The EMBO Journal – found that it does that by hijacking a receptor complex.

“We used super-resolution microscopy to show that a receptor called Synaptotagmin 1 binds to two other previously known clostridial neurotoxin receptors to form a tiny complex that sits on the plasma membrane of neurons,” University of Queensland neurobiologist Professor Frederic Meunier said.  

“The toxin hijacks this complex and enters the synaptic vesicles which store neurotransmitters critical to communication between neurons.

“Botox then interrupts the communication between nerves and muscle cells, causing paralysis.”

The researchers showed that for the Botox toxin to enter the neuron this triple receptor combo is required. When the toxin was bound to just one alone, it wasn’t able to sneak in. When the team got rid of one of the receptors – the Syt1 receptor – entirely, the cell formed a tube to let in the toxin, but never broke from the surface. Think of this a bit like blowing bubbles, but the bubble never detaches from the wand.

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Unfortunately, a carefully measured Botox injection isn’t the only way we can end up with a dose of botulinum toxin. The bacterium Clostridium botulinum which produces the neurotoxin can end up in food, or being breathed in through soil particles or water. It can also directly enter a wound if you’re particularly unlucky.

Even with antitoxins available, the illness – called botulism – kills around 7 percent of people infected.

The team of researchers hope that this new research will allow better treatments for the disease. “Now we know how this complex allows the toxin internalization, we can block interactions between any two of the three receptors to stop the deadly toxins from getting into neurons,” Professor Meunier said.

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