Protein Protects Against Nerve Degeneration

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Protein Protects Against Nerve Degeneration

http://www.medicalnewstoday.com/medicalnews.php?newsid=57945

A protein called NMNAT protects against nerve cell degeneration in

fruit flies and mice, said Baylor College of Medicine researchers in

a report in the Public Library of Science Biology that appears

online.

The finding begs the question if a drug might be developed that

could stimulate extra protein production and thus neuronal

protection - both in injured cells and in those degenerating because

of disease, said Dr. Hugo Bellen, the paper's senior author,

director of the BCM Program in Developmental Biology and a

Medical Institute investigator. While more work needs to be

done to determine whether that would be desirable, Bellen said the

finding is an important one because it identifies NMNAT as essential

in the life of the body's neurons.

Much of the work described in the paper was done by its first

author, Dr. R. Grace Zhai, a postdoctoral fellow in Bellen's

laboratory.

The story began two decades ago when researchers in the U.K.

discovered a mouse whose injured nerve cells were slow to die. Even

when the nerve was cut, it had some function two weeks later while

in a normal mouse injured nerves are non-functional within two days,

said Bellen.

Five years ago, researchers discovered that the mice had three

copies of a gene for a protein that was a fusion of NMNAT and

another protein. Bellen and his colleagues sought to determine

whether NMNAT was actually protective by studying mutant forms of it

in fruit flies or Drosophila melanogaster, a commonly used model

organism. NMNAT exists in a single state in the fruit fly, and there

is only one form of it.

When Zhai, Bellen and colleagues bred flies that lack the protein in

their visual system, they found that the neurons degenerated very

rapidly. However, the degeneration could be slowed by keeping the

flies in the dark and preventing their visual neurons from

activating.

" In the absence of the NMNAT protein, the photoreceptors in the eye

develop normally. They send out axons (tendril extension of the

nerve that grow into the brain) and make synapses (the functional

connection between a nerve axon and the target cell), " said Bellen.

However, late in the development of the eye, the insects in the

pupal stage begin to sense light. As the neurons become active, they

degenerate rapidly. Within two weeks after birth, there are almost

no neurons left.

" Here is a case where the protein is required for the maintenance of

the neuron, " said Bellen.

When flies were raised in the dark, the neurons died, but at very

slow pace when compared to those exposed to light.

" Activity clearly causes a massive degeneration, " he said.

When they exposed flies that made large quantities of NMNAT in the

eye to bright sunlight for 30 days, they found that only 20 percent

of the neurons died - not the 80 percent that would have been

expected.

" This protein can delay the neuronal degeneration process if it is

present at a high level, " said Bellen.

They also found that NMNAT alone and not the enzyme partner found in

mice and other vertebrates was sufficient to protect the neurons.

Bellen said more work needs to be done to identify the mechanisms at

work in the neuronal protection and to determine how to prompt cells

to increase productions of the protein.

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Others who participated in the research include Drs. Yu Cao, P.

Robin Hiesinger, Yi Zhou, Sunil Q. Mehta, L. Schulze and

Patrik Verstreken, all of BCM.

Support for this study came from the Medical

Institute.