London: Researchers at Washington University School of Medicine in St. Louis have for the first time identified a gene that pulls the plug on ailing nerve cell branches from within the nerve cell, which may trigger the painful condition known as neuropathy.

The researchers have shown that blocking the dual leucine zipper kinase (DLK) gene inhibits degeneration of ailing nerve cell branches, and believe that this may help prevent neuropathy.

Neuropathy is a side effect of some forms of chemotherapy and can also afflict patients with cancer, diabetes, kidney failure, viral infections, neurodegenerative disorders and other ailments.

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"Neuropathy can become so extraordinarily painful that some patients stop taking their chemotherapy, regardless of the consequences in their fight against cancer. So we're very excited about the possibilities this gene may offer for reducing that pain," Nature magazine quoted co-senior author Dr. Aaron DiAntonio, associate professor of developmental biology, as saying.

While experimenting on mice, the researchers found that the long axons of the sciatic nerve in the animals with a mutated DLK gene resisted degeneration after it was surgically cut.

In follow-up tests, the researchers took nerve cells in culture and treated their axons with the chemotherapy drug vincristine.

They observed that normal axons degenerated rapidly after exposure to the drug, but axons where DLK's activity had been blocked were protected from degeneration.

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"The pain of neuropathy is often a key factor that limits the dose in cancer chemotherapy. We know when patients are going to start their treatment, so one day it might be possible to start patients on a DLK-blocking drug before their chemotherapy and spare them considerable pain," DiAntonio says.

"We want to fully understand the chain of molecular reactions that carry out DLK's decision, because that might reveal a better opportunity to block the effect with a drug," the researcher adds.

The researchers are planning to study whether blocking DLK stops neurodegeneration in other forms of injury and stress, including the harm inflicted on the optic nerve by glaucoma and central nervous system phenomena like stroke and Parkinson''s disease.

The findings have been published online in Nature Neuroscience.

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