Researchers have deciphered new mechanisms that enable the regeneration of nerve fibers, which they suggest could lead to new treatment approaches to brain, optic nerve, and spinal cord injuries (SCI).

The team, from the Department of Cell Physiology at Ruhr-Universität Bochum (RUB) and led by Professor Dietmar Fischer, report their research in Nature Communications Biology.

Injuries to nerve fibers in the brain, spinal cord, and optic nerves usually result in permanent functional losses as the nerve fibers, called axons, are unable to regenerate following the injury.

“It is possible to partially restore the regenerative capacity of nerve cells in the central nervous system by eliminating the inhibiting protein PTEN,” Fischer explains, in a media release from Ruhr-University Bochum.

“However, a knockout of this kind also triggers many different reactions in the cells at the same time, which often lead to cancer.”

As a result, the direct inhibition of this protein is not suitable for therapeutic approaches in humans. What’s more, the originally postulated mechanism underlying the renewed regenerative capacity following PTEN knockout could not be confirmed in further studies, causing the researchers to seek alternative explanations.

While investigating this as-yet unclear mechanism, the Bochum-based researchers were able to demonstrate that PTEN knockout significantly inhibits an enzyme called glycogen synthase kinase 3, GSK3 for short. This enzyme, in turn, blocks another protein called collapsin response mediator protein 2, CRMP2. This means that the PTEN knockout prevents CRMP2 from being inhibited by GSK3, the release explains.

“If we directly prevent this second step, ie, stop the inhibition of CRMP2, we can also achieve the regeneration-promoting effect in a more specific manner,” Fischer adds.

The activation of CRMP2 itself is not known to have any carcinogenic effect.

“Although we have so far only shown these effects in genetically modified mice and using gene therapy approaches, these findings open up various possibilities for the development of new drug approaches,” he notes.

Further studies in his department are investigating these options, the release concludes.

[Source(s): Ruhr-University Bochum, EurekAlert]