( p> But the mutant Wlds protein doesn'...)Salk and Stanford teams join forces to reveal two paths of neurodegeneration

But the mutant Wlds protein doesn't hamper the wiring process in developing brains. In newborn Wlds mice, axons extending from nerve cells (called RGCs) in the retina to a brain center called the superior colliculus were still undergoing their normal pruning process, the Salk researchers observed,

These findings show that axon degeneration after injury or developmental pruning requires different activities. "Superficially they look the same," says O'Leary, "but our studies show that they are mechanistically different, at least at the initial stages."

Thinking this could be age-related, McLaughlin cut the same axons in newborn Wlds mice and found that degeneration was slowed. "When I saw RGC axons in the superior colliculus that appeared morphologically perfect five days after they had been completely separated from RGCs, I was thrilled," says McLaughlin.

Meanwhile at Stanford, Luo's graduate student and co-lead author Eric Hoopfer together with McLaughlin, made "transgenic" fruitflies carrying the Wlds gene and found it had no effect on axon pruning during development, but that it did slow degeneration in cut axons ?just like in mice.

Hoopfer explains that an early hypothesis was that "the axon degeneration at the heart of neurodegenerative diseases may be a misuse of normal pruning programs, but our studies suggest that two different mechanisms are involved."

According to Luo, these findings also suggest strategies to slow neurodegeneration. "Wlds protein protects axons after injury and has been shown to be effective in delaying degeneration not just after injury, but in diseases similar to Parkinson's disease or motor neuron injury," he explains.

Luo and O'Leary believe that the conservation of the differences in axon degeneration between developmental pruning and injury from flies to mammals points to general mechanisms which are most likely also at work in the human nervous system. Both investigators bel
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Source:Salk Institute