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Scientists achieve 'Holy Grail': figuring out the nerve-muscle=20
connection
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Copyright =A9 1996 Nando.net Copyright =A9 1996 The Associated Press
BOSTON (May 16, 1996 6:12 p.m. EDT) -- Scientists have unraveled the
mysteries of one of life's most basic pieces of wiring -- the=20
connection between nerves and muscles.
Every time someone twitches a toe or wiggles a finger, the nerves
communicate with the muscles. But just how the body constructs the
biological machinery that makes this happen, usually flawlessly, has=20
been unclear.
"This is the most intensively studied communications relay point in=20
the human body," said Dr. George Yancopoulos. "Understanding it is a=20
Holy Grail."
Now Yancopoulos and another team, working independently, have produced
three reports published Thursday that provide the most detailed=20
picture yet of this incredibly complex system.
The discovery may offer clues about how cell-to-cell communication=20
goes on inside the brain, and it could also lead to new treatments for=20
nerve injuries and a variety of diseases such as myasthenia gravis=20
that occur when these cell connections become garbled.
Further, the research may yield a remedy for muscle atrophy that=20
occurs when people break bones or become bedridden.
Nerve cells talk to each other, as well as give orders to muscles, by
sending messages across gaps called synapses. The new work shows how=20
these synapses are formed where nerve meets muscle, a point called the
neuromuscular junction.
"If cells connected to each other willy nilly, they would work about=20
as well as a radio if the wires were soldered at random," said Dr.=20
Joshua R. Sanes of Washington University in St. Louis, another of the=20
researchers.
Instead, nerves and muscles create chemically intricate synapses in=20
just the right places. The secret, it turns out, seems to be two=20
proteins -- one called agrin and another known as=20
muscle-specific-receptor kinase, or MuSK.
Sanes and colleagues looked at the role of agrin, while Yancopoulos=20
and others from Regeneron Pharmaceuticals Inc. of Tarrytown, N.Y.=20
examined agrin's interaction with MuSK. Their reports were published=20
in the journal Cell.
Both worked with mice that were missing the genes that produce agrin=20
or MuSK. They found that both proteins are necessary during embryonic
development to make working connections between nerves and muscles. If
either is missing, the effect is the same: The mice are unable to move=20
or breathe and die shortly after birth.
A major problem in treating nerve injuries is getting the nerves to=20
grow back and work properly. Dr. Zack W. Hall, director of the=20
National Institute of Neurological Disorders and Stroke, said the=20
latest studies bring scientists a step closer to solving this.
"The problem with regeneration is trying to recreate those embryonic
conditions in which they were formed in the first place. The more we=20
know about this, the better we can encourage that regeneration," he=20
said.
During development, it now appears that nerve cells grow toward=20
muscles and then release agrin. On the muscle side of the gap, the=20
agrin is received by MuSK, which works in combination with another=20
protein called muscle-associated specificity component, or MASC.
This triggers a complicated chain reaction that eventually results in
changes in both the nerve and the muscle that add up to a working=20
synapse.
When this system is up and running, the nerve cells talk to the muscle
cells by sending a chemical code in the form of the neurotransmitter
acetylcholine.
Agrin is the first step. It signals the muscle to pull together the
chemicals it needs to construct acetylcholine receptors so it can=20
receive these messages.
Regeneron scientists say agrin works like a muscle growth hormone, and=20
it might be used as a medicine for some muscle conditions.
When people break bones and have to be immobilized, their muscle=20
quickly begins to atrophy. The Regeneron researchers have produced the=20
human form of agrin and are testing whether it can halt this muscle=20
breakdown.
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