Botox – Turn that Frown Upside Down?

Nearly everyone has heard of Botox – but not that many people know exactly how it works. Enter the Antisense Scientists!

needle

Botox, Bacteria and Botulism.

The Botox formula actually contains a neurotoxin called botulinum toxin, which is naturally produced by the bacterium Clostridium botulinum. This bacteria is actually responsible for botulism – a potentially fatal illness where ingested C. botulinum produce a number of toxins (including the botulinum neurotoxin used in Botox), which leads to gradual paralysis of the body’s systems. If the disease progresses to paralyse the lungs, respiratory failure leads to the death of the individual. The Botox formula harnesses the power of the neurotoxin, which is then used to paralyse wrinkle-causing muscle.

How the Toxin Works

Neurotoxins work by disabling neurons – the cells of the central nervous system that control muscles (like the ones in our face that may or may not be causing wrinkles). Neurons send signals by using electrical currents which pass quickly through the nervous system. Signals are passed between neurons using chemical messengers called neurotransmitters, which are delivered from the site of release (at the end of one neuron), and received at the top of the next neuron (like in the diagram below).

botox 1

Normally, as the electrical signal reaches the end of the first neuron, neurotransmitter is signalled to be released. Neurotransmitter is contained within small balls called vesicles, which are then trafficked to the membrane of the neuron; the vesicle fuses with the membrane and the contents are released. The neurotransmitter can then travel across the space between the neurons and bind to receptors on a second neuron, inducing a signal in that neuron. The same essential mechanism is used to allow neurons to communicate with muscle where, instead of a second neuron, the receptors for the neurotransmitters are on a muscle. The reception of neurotransmitters leads to muscle contraction. These connections are known as neuromuscular junctions.

At the neuromuscular junctions the neurotransmitter is acetylcholine. Critically, the fusion of the vesicles with the membrane to allow acetylcholine release is mediated by proteins called SNAP and SNAREs, which essentially help to hook and anchor the vesicles to the membrane to then allow fusion and release of acetylcholine.  The light chain portion of botulinum toxin cleaves SNAP-25, one of those key anchoring proteins, leading to loss of normal acetylcholine. No acetylcholine release means no reception by the muscle, which means no muscle contraction – all leading to muscle paralysis. When injected into the face, this causes relaxation of wrinkle-causing muscles.

Non-Cosmetic Botox Uses

It might surprise you to find that botulinum toxin may well have a number of potential other uses. The toxins can be used to relieve headaches, pelvic pain, back pain, as well as pain following stroke and cancer therapies. These therapies are less well known and established than the traditional wrinkle-busting role of Botox, but have been used to improve the quality of life of many patients!

 

 

Robb

References

Wheeler A, & Smith HS (2013). Botulinum toxins: mechanisms of action, antinociception and clinical applications. Toxicology, 306, 124-46 PMID: 23435179

Images: http://www.drforrester.co.uk, http://idontblog.ca/to-botox-or-not-to-botox/

Additional References: http://www.nhs.uk/conditions/botulism/Pages/Introduction.aspx

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