Enzyme could help regeneration of nervous systems, study finds

A partly EU-funded team of UK and US researchers has identified an enzyme that plays a key role in the regeneration of nerve fibres (axons) after injury. Mammalian sterile 20-like kinase-3b (Mst3b) was shown to increase axon growth in the central nervous system (CNS) as well as the peripheral nervous system (PNS). The research results, now published in Nature Neuroscience, could open up new possibilities for treating stroke, spinal cord injuries and traumatic brain injury.

The lead author of the study, Dr Barbara Lorber, received financial support from the AXON GROWTH KINASE (Role of N-kinase in regulating central nervous system regeneration) project. The Marie Curie Outgoing International Fellowship enabled Dr Lorber, originally working in the University of Birmingham in the UK, to take her research to the renowned Children's Hospital Boston, US.

Mst3b was previously known to regulate axon outgrowth in embryonic cortical neurons in cell cultures. This new study confirms that it has a similar function in mature nervous systems. Normally, the CNS cannot regenerate injured nerve fibres, limiting people's ability to recover from brain or spinal cord injuries.

Working with live rats whose optic nerve was damaged, the researchers observed that axon regeneration increased when Mst3b was present in the neurons. When the enzyme was absent, however, axons showed very little regeneration. Once the enzyme is activated, it in turn activates signals that switch on the genes necessary for axons to grow.

"Axon regeneration occurs readily after injury in the mature PNS [...], but not within the CNS," the paper reads. "The optic nerve is a classic model of a CNS pathway that does not regenerate when injured."

"We have shown that Mst3b [...] is a key regulator of axon regeneration in the adult optic nerve and radial nerve," the paper concludes. "It will be important to investigate whether Mst3b regulates axon regeneration in other parts of the CNS and PNS, and whether expression of a constitutively active form of Mst3b can augment the limited amount of growth that is at present achievable after CNS injury. These and further studies into the molecular mechanisms by which Mst3b functions may open up new avenues for the treatment of CNS injuries."

Future research will have to determine whether Mst3b is the best stimulator of axon growth from a practical drug-development standpoint, the researchers say.

The AXON GROWTH KINASE fellowship was funded under the Sixth Framework Programme (FP6) to the tune of EUR 250,000. It focused on the role of Mst3b in optic nerve regeneration in vivo.

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