Breakthrough Reveals How Botox Infiltrates Brain Cells
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Scientists at the University of Queensland have made a breakthrough in understanding how the drug and ubiquitous cosmetic treatment Botox penetrates brain cells. Their study was published in The EMBO Journal.
Botox: from bacteria to beauty
Led by Professor Frederic Meunier and Dr. Merja Joensuu from the Queensland Brain Institute at the University of Queensland, the team identified the precise molecular pathway through which the botulinum neurotoxin type-A, commonly known as Botox, gets into neurons.
Botox has a long history in medicine – originally developed to alleviate symptoms of the eye condition strabismus, its muscle-freezing properties have been used to treat spasms, migraine and even excessive sweating. Perhaps Botox’s most well-known use is in the cosmetics industry, where it is injected to smooth wrinkles. When botulinum toxin is released by the bacterium Clostridium botulinum, it can cause the disease botulism.
Treatments for botulism
Employing super-resolution microscopy, the researchers demonstrated that a receptor called synaptotagmin 1 combines with two previously identified clostridial neurotoxin receptors, forming a minute complex situated on the surface of neurons. “The toxin hijacks this complex and enters the synaptic vesicles which store neurotransmitters critical to communication between neurons," said Meunier.
“Botox then interrupts the communication between nerves and muscle cells, causing paralysis,” he added.
This newfound understanding of Botox's entry mechanism opens the door to identifying new treatments for botulism, which is a potentially life-threatening bacterial infection that is often contracted after eating poorly canned food that has been contaminated with C. botulinum.
“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,” Meunier said.
The study answers a key question about the drug that had proved difficult to solve. “Clostridial neurotoxins are among the most potent protein toxins known to humans,” Dr Joensuu said. “We now have a full picture of how these toxins are internalised to intoxicate neurons at therapeutically relevant concentrations.”
Joensuu M, Syed P, Saber SH, et al. Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG-Syt1-SV2 plasma membrane nanocluster for synaptic vesicle entry. The EMBO Journal. 2023:e112095. doi:10.15252/embj.2022112095
This article is a rework of a press release issued by the University of Queensland. Material has been edited for length and content.