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Pinpointing the protein problem in Lou Gehrigs Disease

TROY, NY The cause of Lou Gehrigs Disease (ALS or amyotrophic lateral sclerosis) has remained elusive since it brought down one of baseballs greatest players 60 years ago.

According to Wilfredo Freddie Coln, ALS starts when good proteins go bad. Understanding just why they go bad is a necessary first step toward developing medicines that will help ALS patients live with a manageable disease instead of a death sentence.

The Rensselaer biochemists vital research has recently earned a $1 million, four-year grant from the National Institutes of Health.

The NIH grant will support Colons study of the hereditary version of the disease, called familial ALS or FALS. He is attempting to understand why mutants of the enzyme superoxide dismutase (SOD1) fail and misfunction in FALS.

On average, FALS strikes people who are around 47 years of age, says Colon. Most patients die within two to five years. But some patients, whose proteins exhibit a different kind of mutation, experience a very slow progression and can survive for as long as 18 years, says Coln.

The existence of SOD1 mutants associated with this milder form of FALS makes it an intriguing biophysical and biochemical marker. Unlocking the mystery of the pathogenic causes for FALS could also play an important role for better understanding other neurogenerative disorders, such as Parkinsons and Alzheimers.

SOD1 is an enzyme that normally breaks down free radicals, highly reactive molecules that quickly damage DNA and proteins, thereby, endangering cells. However, the genetic defect that results in SOD1 mutations does not cause FALS because the normal function has been affected. Instead, a new mysterious toxic function of SOD1 leads to the death of motor neurons.

Faulty SOD1 behavior, caused by a number of different genetic mutations, is at the root of roughly one-fifth of inherited or familial ALS (FALS) cases. Around 10 percent of ALS cases are familial (FAL
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Contact: Megan Galbraith
galbrm@rpi.edu
518-276-6050
Rensselaer Polytechnic Institute
22-Mar-2002


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