Motor neurone communication could hold the key to sustaining a fading signal

On Tuesday morning we received an email from The Scotsman – a Scotland based newspaper asking us for a quote on a new research finding that has possible implications for MND research. We’ll keep our fingers crossed that Brian’s quote (given at the bottom of this blog post) is included in The Scotsman tomorrow!

The study in question found that a protein called TGFβ2 plays a vital role in boosting signals from nerve cells to the muscle. It was led by researchers in Aberdeen, Scotland and Otago, New Zealand and was published in the journal PNAS.

How do motor neurones communicate with muscle?
Motor neurones exist in our bodies to pass on messages from the brain to our muscles to allow us to move. From the brain, a signal is sent down the motor neurones via a ‘Mexican wave’ mechanism until it can go no further. Once at the end of a neurone it is then faced with the challenges of changing the signal into something that the muscle can understand. It then has to send it out of the neurone towards the muscle by bridging a gap known as the ‘neuromuscular junction’. This may sound relatively simple to do, but bear in mind that our bodies do this via a series of automatic mechanisms that do not rely on brain processing and it gets a lot more complicated!

The way our bodies face these challenges is by the original signal triggering the release of a ‘muscle talking’ chemical (known as Acetyl Choline) into the gap. The muscle receiving the signal then has to collect enough of the chemical before it can ‘hear’ what to do and start its own mechanisms to make the muscle move.

Understanding the intricate detail of these processes and how they are regulated is important in being able to be able to design future therapies that can keep the ‘move’ signal going through the development of MND.

So what do we already know about TGFβ2?
Researchers have known for a while that TGFβ2 is found in our muscles, but its role was not really understood. We also know from two studies published in 2005 and 2006 that if mice that model MND are given TGFβ2, an increased muscle function but no increase in survival can be seen. The reasons why this happened were also not fully understood.

What did the researchers find in this study?
This collaborative research group have begun to unravel how TGFβ2 plays a role in sustaining a signal sent from motor neurones to the muscles.

It does this by acting as a signal booster to increase the amount of signal being sent through the gap per trigger. This therefore means that its effect on the symptoms of MND may be explained by needing less triggers to be ‘heard’ by the muscle which would lead to an increased muscle function even when surrounding motor neurones are degenerating. As its mechanism of action does not target the cause of MND, this also explains why TGFβ2 does not have an effect on survival. Even though TGFβ2 is toxic in humans, understanding the mechanism for how it works can lead to the development of other treatments that can act on this process.

What does this mean to the future of MND research?
In our statement to The Scotsman, Dr Brian Dickie explained that “treatment of complex diseases like MND may require sophisticated treatment approaches, possibly involving a cocktail of drugs, attacking the disease process in different ways, at different stages.

“These findings suggest that the process of keeping nerve cells performing their basic function will be important, in combination with other approaches to stop the nerves from degenerating.”  

PNAS Journal article published online ahead of print on 12 July 2010:
TGF-β2 alters the characteristics of the neuromuscular junction by regulating presynaptic quantal size.

One thought on “Motor neurone communication could hold the key to sustaining a fading signal

  1. We have just opened West Sussex South’s Website, |I will make sure they know about this…..sounds very exciting, then I am an incurable optimist, as is , I understand from Patrick, so is Dr. Brian Dickie! Julia Franklin

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