Could CNS damage be repaired by controlling signals in nerve cells?

Could CNS damage be repaired by controlling signals in nerve cells?

Scientists in Aberdeen are carrying out research to see whether modifying chemicals and proteins – signaling molecules – within nerve cells could help repair damage to the human central nervous system (CNS).

Most cells in the human body have the ability to repair themselves. For example, if you cut your finger, in most cases, it will eventually heal.

However, if our CNS suffers injury - perhaps after a road accident or a fall like the riding disaster suffered by the late actor Christopher Reeve; or following a stroke or the onset of neurodegenerative disease - it is unable to repair itself.

This may be because the body could suffer even more if nerve processes in the brain and spinal cord - which together make up the CNS - are wrongly re-connected.

The CNS is made up of a variety of cells and tissues that make many proteins that prevent the regrowth of damaged nerve processes, known as axons. For years, researchers have tried to identify these "inhibitory" proteins.

Attempts have been made to overcome the inhibitory nature of the CNS by using invasive methods such as grafting tissues or cells into the site of the injury, killing inhibitory cells, using antibodies to block inhibitory proteins and knocking out genes that produce inhibitory proteins.

Although some success has been achieved in laboratory studies, there remains no definitive clinical treatment for effective CNS repair.

Now researchers at the University of Aberdeen, led by Dr Derryck Shewan from the School of Medical Sciences, are taking a totally different tack.

Dr Shewan said: "We know that nerve cells - or neurons as they are known - can grow and thrive in the embryonic CNS environment where older neurons fail to regenerate. Embryonic neurons can also grow axons in the adult CNS.

"This suggests that something happens to the neurons when they age which make them more susceptible to the hostile CNS environment.

"We want to see if we can find a way of getting older nerve processes to behave more like their younger counterparts, by manipulating signaling molecules within the nerve cells rather than the environment around them.

“This could allow the axons to overcome multiple inhibitory signals all at the same time. If we can do this it raises the tantalising possibility that more effective CNS repair may be achieved using less invasive methods than many other strategies to date."

The charity Tenovus Scotland has backed the research team’s work which includes studying a chemical called cyclic AMP which occurs naturally in the body. Cyclic AMP is found in much higher levels in embryonic nerve cells, which are able to regenerate, than in older nerve cells, which cannot. Stimulating cyclic AMP improves axon regeneration and allows axons to overcome inhibitory signals.

However as Cyclic AMP is a hugely important chemical in the body because it is found in all cells and is involved in a wide variety of cellular functions, the Aberdeen team wishes to look for other signaling molecules that may be more appropriate to target.

Dr Shewan explained: “We just don’t know what repercussions or possible side effects of tampering with cyclic AMP could bring to nerve cells and other types of cells that also need cyclic AMP to function normally.”

“We need to establish new avenues of research to find out if other signaling molecules might be targeted to improve axon regeneration without the potential widespread repercussions that could result from tampering with cyclic AMP. The Tenovus Scotland support will help us begin this search. “

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