Scientists identify master enzyme for regenerating nerve fibers in live animals

WASHINGTON - A previously identified enzyme, known as Mst3b, has been found to play a major role in regenerating damaged axons (nerve fibers) in a live animal model, in both the peripheral and central nervous systems, according to researchers at Children’s Hospital Boston.

The findings indicate that Mst3b - or agents that stimulate it - could be a possible means of treating stroke, spinal cord damage and traumatic brain injury.

Normally, neurons in the central nervous system (the brain and spinal cord) cannot regenerate injured nerve fibres, limiting people’s ability to recover from brain or spinal cord injuries.

Led by Dr. Nina Irwin and Dr. Larry Benowitz, the study builds on their previous discoveries.

In 2002, they showed that a naturally occurring small molecule, inosine, stimulates axon regeneration, later showing that it helps restore neurological functions in animal models of injury.

In 2006, they reported a previously unknown growth factor, oncomodulin, to have dramatic effects on axon growth.

Investigating the mechanisms of action of inosine and oncomodulin, the researchers found that both compounds activate Mst3b- an enzyme that appears to be a master regulator of a cell-signaling pathway controlling axon growth.

Mst3b, a protein kinase, in turn activates signals that switch on the genes necessary for axons to grow.

Working with live rats whose optic nerve was damaged (a common model of central-nervous-system injury), the researchers showed that in the absence of Mst3b, axons show very little regeneration, even in the presence of factors known to enhance axon growth.

In cell cultures, axon growth increased when activated Mst3b was expressed in the neurons.

“All the growth factors we’ve tested - oncomodulin, inosine, brain-derived neurotropic factor, nerve growth factor - act through Mst3b. In fact, activating Mst3b by itself is enough to cause growth even if there are no growth factors around. In terms of basic understanding of nerve cells, this is a very exciting finding,” Nature quoted Benowitz as saying.

Further studies examining how Mst3b exerts this growth-promoting effect may open up new avenues for treating brain and spinal cord injuries, says Benowitz.

The study has been published in Nature Neuroscience. (ANI)