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Old 05-09-2007, 07:13 AM #1
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Default Scientist say protein may be the key to fatal motor neuron disease

Piece of ALS puzzle eyed
Scientist say protein may be the key to fatal motor neuron disease
BY JAMIE TALAN
jamie.talan@newsday.com

May 9, 2007

Scientists studying amyotrophic lateral sclerosis, the disease that killed baseball star Lou Gehrig, have identified a protein that may be responsible for the fatal motor neuron disease in people with no family history of it - the majority of cases. Unraveling the link between the protein and the disease could lead to new treatments.

"This finding is of fundamental importance," said Dr. Lewis P. Rowland, a professor of neurology at Columbia University Medical Center who has been treating ALS patients for decades. "The question now is what does this protein do."

The protein is called TDP-43, and the first hint that it is linked to ALS came last year after a team of investigators at the University of Pennsylvania School of Medicine found it in the brains of people who had died of a non-familial form of ALS.

In the latest study, published this month in the Annals of Neurology, University of Pennsylvania researchers John Trojanowski and Virginia Lee collaborated with Ian Mackenzie of the University of British Columbia and others to replicate the TDP-43 finding in postmortem ALS brains.

Trojanowski and Lee are pioneers in neurodegenerative diseases, working together to unravel the biochemical underpinnings of Alzheimer's, Parkinson's and now ALS.

For more than a decade, scientists have been studying another protein called SOD-1 that causes the familial form of ALS. The SOD-1 genetic mutation accounts for about 1 percent of all ALS cases. SOD-1 has been a major target for treatments. Currently, nothing slows or stops the damage to motor neurons that leads to paralysis and death.

Identification of TDP-43 will provide scientists with a new therapeutic target. And figuring out what it does to trigger damage of the motor neurons - the cells that allow the brain to talk to the body - could yield ways to prevent the damage.

Lee explained that it is not clear how the protein works to damage motor neurons. Normally, the protein binds to single strands of DNA and interacts with a number of other proteins. It's also involved with the transport of other substances throughout the body. But in ALS brains, those cells that are damaged by the disease are void of the protein in the cell nucleus. This could render it unable to perform its many crucial actions, Trojanowski said.

This same protein is also found in the brains of people who died with frontotemporal dementia, a progressive brain disease that can radically impair a person's ability to think and behave.

The Pennsylvania researchers are making animal models with too little and too much protein to see whether they can induce symptoms of ALS.

This finding also unearthed a very important piece of the ALS puzzle. While scientists have long believed that ALS patients became trapped inside of their bodies with a mind fully spared by the disease, doctors now believe that many patients may have subtle cognitive or thinking problems that may not have been picked up because the physical disabilities overshadow them.

http://www.newsday.com/news/health/n...y-health-print
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