Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered protein may be key to muscular dystrophy

19.08.2004


A defect in the action of a newly discovered protein may play a central role in muscular dystrophy, a disease of progressive muscle degeneration with no known cure.



Scientists at UCSF’s Ernest Gallo Clinic and Research Center discovered in an animal model of the disease that during periods of intense muscle activity, muscles remain excited too long and degenerate if the protein fails to transport the neurotransmitter acetylcholine away from the nerve-muscle synapse. Muscle degeneration is the hallmark of muscular dystrophy, one of the most common genetic diseases.

The study was carried out in the roundworm, C. elegans, an animal which has provided early clues to the role of a number of important molecules in the human nervous system. The researchers expect that the protein, which they showed is an acetylcholine transporter, plays the same role in humans as it does in C. elegans, identifying a potential new route for treatment of muscular dystrophy.


The research is being reported in the August 19 issue of the journal Nature.

Normally, a nerve cell induces a muscle cell to contract by releasing the neurotransmitter acetylcholine at the synapse -- the junction where the two cells meet. Researchers have identified transporters for most neurotransmitters, such as serotonin, dopamine and glutamate. The transporters remove neurotransmitters from the synapse, in effect providing an "off" switch to the neurotransmitter’s potent effects. It was thought that normal enzymatic breakdown of acetylcholine was so effective that a transporter wasn’t needed to clear excess acetylcholine from the synapse. But the scientists found that during periods of intense muscle activity, a transporter must clear acetylcholine from the synapse.

"Discovering a transporter for acetylcholine was quite a surprise," said Steven McIntire, MD, PhD, UCSF assistant professor of neurology. "Identification of an acetylcholine transporter in mammals could lead to useful therapeutics to treat neuromuscular diseases as well as disorders of the central nervous system." McIntire is a principal investigator at the UCSF-affiliated Gallo Clinic and Research Center, and is senior author on the Nature paper.

Transporters have proven to be important drug targets, McIntire said. Prozac, for example, modulates a transporter that regulates serotonin concentration. Besides carrying messages from nerve cells to muscle cells, acetylcholine triggers communication between neurons in the brain, and is involved directly or indirectly in many diseases, including Alzheimer’s and diseases of peripheral nerves. Discovery of the acetylcholine transporter could lead to therapies for some of these diseases based on altering acetylcholine levels, he said.

Duchenne muscular dystrophy, the most common form of the disease, primarily affects boys -- about one in 3,500 male births. It typically begins in early childhood. Children often experience leg weakness, falling and progressive loss of movement, eventually becoming wheel chair-dependent. Many die in their late teens or early twenties. Currently, there is no cure.

Scientists already knew that muscular dystrophy results from genetic defects in components of a network of proteins, known as the dystrophin-glycoprotein complex (DGC),that extends through the entire muscle cell membrane, linking the framework inside the cell to the region outside of the cell. The complex is found in C. elegans, in mice and in humans. In each species, defects in the complex can cause muscle degeneration, but the exact role of the complex in disease has not been clear.

In a genetic screen, the scientists identified 12 mutations which produced defects in coordinated movement just like those found in C. elegans DGC mutants -- a model for human muscular dystrophy. While seven of the mutants involved defective DGC function, five others resulted from variations in a previously unidentified gene. The team cloned this gene, snf-6, and found that its sequence was similar to genes in a family of mammalian neurotransmitter transporters. Because analysis of mutants indicated defects in acetylcholine activity, they tested whether the expressed protein, SNF-6, transports acetylcholine in mammalian cells grown in culture. They found that it is indeed an acetylcholine transporter.

The team used fluorescence techniques to determine that the distribution of SNF-6 was altered in DGC mutants. They found that the DGC, imbedded in the muscle cell membrane, maintains the neurotransmitter transporter at the neuromuscular synapse. In this location, the transporter is available to clear excess acetylcholine.

Further studies confirmed that when acetylcholine transporter function is disrupted, whether by defects in the DGC protein complex that maintains the transporter, or by genetic defects in the transporter itself, the result is muscle degeneration typical of muscular dystrophy.

"We hope that these findings will ultimately lead to an effective treatment for common forms of muscular dystrophy," McIntire said.

Wallace Ravven | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie

nachricht Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New studies increase confidence in NASA's measure of Earth's temperature

A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.

The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...

Im Focus: The geometry of an electron determined for the first time

Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.

The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

On Mars, sands shift to a different drum

24.05.2019 | Physics and Astronomy

Piedmont Atlanta first in Georgia to offer new minimally invasive treatment for emphysema

24.05.2019 | Medical Engineering

Chemical juggling with three particles

24.05.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>