The gene which “pulls the plug” on ailing nerve cell branches from within the nerve cell has recently been identified by researchers at Washington University School of Medicine in St. Louis. This gene, known as the dual leucine zipper kinase (DLK) gene, is thought to possibly trigger a condition known as neuropathy. Neuropathy is a side effect of some forms of chemotherapy and can be so extremely painful that patients some patients stop taking chemotherapy. It has been know since 1850 that nerve cells have been able to cut off axons which are damaged and is a normal part of early human development. It is the inappropriate loss of axons in the adult nervous system however which causes the excruciating pain known as neuropathy.
Diagram 1: Human neuron
The co-senior author of the research paper Aaron DiAntonio, M.D., Ph.D., associate professor of developmental biology had previously revealed that the fruit fly's version of DLK helps establish synapses, junctures where two nerve cells communicate. But they found the gene doesn't do the same thing in mice. This spiked the attention of one of DiAntonio’s students Bradley Miller, who was curious as to DLK’s role in mammals. He then consulted with co-senior author Jeffrey Milbrandt, M.D., Ph.D., the David Clayson Professor of Neurology. They then showed that, after being surgically cut, the long axons of the sciatic nerve in mice with a mutated DLK gene had resisted degeneration. Miller and Craig Press, who was a M.D. /Ph.D. student in Milbrandt’s lab, conducted some follow-up tests which took nerve cells in culture and then treated their axons with the chemotherapy drug vincristine. They then found that the axons with blocked DLK had been blocked were protected from degeneration whereas normal axons were rapidly degenerated after being exposed to the drug.
DLK does not actually destroy the damaged axons but rather it starts the process which does the destroying. The chain of molecular reactions is still not yet fully understood but once it is, it is thought that there will be a better opportunity to block the effect of DLK by a drug. DiAntonio and Milbrandt also have plans to test if the blocking of DLK is successful in stopping neurodegeneration in other forms of injury and stress.
References:
Source: Medical News TODAY. Title: Painful nerve condition may be improved by blocking protein Link: http://www.medicalnewstoday.com/articles/142503.php
Source: EurekAlert Title: Blocking protein may help ease painful nerve condition Link: http://www.eurekalert.org/pub_releases/2009-03/wuso-bpm031309.php
Source: Breakthrough Digest Title: Blocking protein may help ease painful nerve condition Link: http://www.breakthroughdigest.com/neuropathy/blocking-protein-may-help-ease-painful-nerve-condition/
Diagram 1: Human neuron diagram from article Fun Science - How many megabytes in the human body? Link: http://www.utheguru.com/fun-science-how-many-megabytes-in-the-human-body
