Next time you are about to swat a fruit fly, consider this: the common fly is one of the best tools we have for studying disease. About 75 percent of known human disease genes have a match in the genome of flies; half of fly proteins that have been sequenced have mammalian homologs, which you might think of as identical blueprints.
The lowly fly has been well studied for over 100 years, and is the center of much work on neurodegenerative disease and trauma, including Huntington’s and Parkinson’s, as well as spinal cord injury.
The basic idea is that if it is possible to understand biological pathways involved in maintaining healthy nerves, and how well-orchestrated processes clear away damaged ones, that may offer targets for drugs or therapies to rescue nerves and promote recovery.
To the point: a group at the University of Pennsylvania and the Howard Hughes Medical Institute there published a paper this week about an enzyme that appears to be vital in protecting nerves. They call the enzyme Nmnat, (that is short for nicotinamide mononucleotide adenylyltransferase, and pronounced just the way it’s spelled...? I’d guess Enem-nat). The work was done in the adult fruit fly, Drosophila melanogaster.
From a Penn press release:
“We are using the basic power of the fly to learn about how neurons are damaged in acute injury situations,” said Nancy Bonini, senior author of the research and a professor in the Department of Biology at Penn. “Our work indicates that Nmnat may be key.”
The research was published in Current Biology
. First author is postdoc Yanshan Fang, with postdoc Lorena Soares and technicians Xiuyin Teng and Melissa Geary.
Bonini explains that when a nerve suffers an injury, its long fiber, or axon, often degenerates. The process by which it dies back is known as Wallerian degeneration and this, she says, is an active, orderly process that while critical, is not fully understood.
Using a fly wing, which it translucent and therefore can easily be dyed to see its living nerves, Bonini’s lab cut axons without killing the fly, thus following the animal’s response to nerve injury for weeks. Yes, the cut wing nerve underwent Wallerian degeneration. They then tested Nmnat and another protein called Wld, which was known to protect nerves from degeneration. The proteins did just what was expected; the nerves were saved.
The researchers also showed that when a mutant fly’s own Nmnat was depleted, the nerves acted as if the axon had been physically traumatized. And when Nmnat and the other “rescue” proteins were added back, degeneration stopped.
How does this rescue work? Bonini’s research suggests that Nmnat may stabilize mitochondria (recall from basic biology that these are the cell’s powerplants, creating energy to operate) in some way in order to keep axons in a healthy state.
From the release:
“We have some hope that these proteins or their activity may someday serve as drug targets or could provide the foundation for a therapeutic advance,” Bonini said. “But right now, my hope is that the power of the fly model will open up a lot of new directions of research and new pathways that could be targets for development in the future.”