Enzyme could lead to a possible treatment for brain and spin

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Enzyme could lead to a possible treatment for brain and spin

Postby ElMarino » Sun Oct 25, 2009 10:16 am

Good news, huh?

Master regulator found for regenerating nerve fibers in live animals
Enzyme could lead to a possible treatment for brain and spinal cord injury


Boston, Mass. -- Researchers at Children's Hospital Boston report that an enzyme known as Mst3b, previously identified in their lab, is essential for regenerating damaged axons (nerve fibers) in a live animal model, in both the peripheral and central nervous systems. Their findings, published online by Nature Neuroscience on October 25, suggest Mst3b – or agents that stimulate it – as 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 fibers, limiting people's ability to recover from brain or spinal cord injuries.

The study, led by Nina Irwin, PhD and Larry Benowitz, PhD, of the Laboratories for Neuroscience Research in Neurosurgery and the F.M. Kirby Neurobiology Center at Children's, builds on previous discoveries in the lab. 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, Benowitz and colleagues reported a previously unknown growth factor, oncomodulin, to have dramatic effects on axon growth.

Investigating the mechanisms of action of inosine and oncomodulin, Irwin and Benowitz discovered 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), Irwin, Benowitz and colleagues show 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," says Benowitz. "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."

Further studies examining how Mst3b exerts this growth-promoting effect may open up new avenues for treating brain and spinal cord injuries, Benowitz says. While this study explains why growth factors work – because they stimulate Mst3b – it's not yet known whether Mst3b is the best stimulator of axon growth from a practical drug-development standpoint, he adds.

Irwin is now working on possible gene therapy approaches involving Mst3b. Activating Mst3b may help overcome some natural "brakes" in the cell-signaling system that prevent nerve regeneration under normal conditions.

###

Barbara Lorber, PhD, formerly of Children's and now at the University of Cambridge (Cambridge, UK), was the paper's first author. NIH, the European Union, Alseres, Inc., and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation funded this study.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 13 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.


http://www.eurekalert.org/pub_releases/ ... 102209.php
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Postby ElMarino » Sun Oct 25, 2009 11:27 am

There's a coi8ncidence, a similar news story posted only hours later..

GAP-43 expression correlates with spinal motoneuron regeneration following root avulsion


The growth-associated protein GAP-43 plays a crucial role in axonal regeneration in injured neurons.

Methods: We have used immunohistochemistry to investigate the expression of GAP-43 in spinal motoneurons during nerve reconstruction following root avulsion in the neonatal and adult rats.

Results: Following the injury, GAP-43-immunoreactivity (IR) could be found in adult avulsed motoneurons as early as 1 day, increased from 3 to 7 days and reached a maximal level at 2 weeks post-injury. The up-regulation of GAP-43 in adult avulsed motoneurons was accompanied with the axonal regeneration indicated by numerous regenerating motor axons entering the reimplanted ventral root and nerve.

In contrastGAP-43-IR could not be found in the neonatal avulsed motoneurons at any examined post-injury time points. This failure of up-regulation of GAP-43 was coincident with no axonal regeneration in the reimplanted nerve in the neonatal rats.

Conclusion: Close association of GAP-43 expression and capacity of regeneration in reimplanted spinal nerve of avulsed motoneurons suggests that GAP-43 is a potential therapeutic target for treatment of root avulsion of brachial plexus.

Author: Qiuju YuanBing HuHuanxing SuKwok-Fai SoZhixiu LinWutian Wu
Credits/Source: Journal of Brachial Plexus and Peripheral Nerve Injury 2009, 4:18


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