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New culprit found in Lou Gehrig's disease
Date:11/21/2011

CHICAGO --- Following a major Northwestern Medicine breakthrough that identified a common converging point for all forms of amyotrophic lateral sclerosis (ALS and Lou Gehrig's disease), a new finding from the same scientists further broadens the understanding of why cells in the brain and spinal cord degenerate in the fatal disease.

Less than three months ago, Northwestern research found that the crucial recycling system for cells in the brain and spinal cord was broken in people with ALS. And one mutated gene had a key role. Like a loafing worker, it wasn't doing its job to recycle damaged cells.

Now, scientists have discovered a second faulty gene -- a new loafing worker -- in the same recycling pathway. The finding is reported in Archives of Neurology.

"Now that we have two bad players, it shines more light on this broken pathway," said senior author Teepu Siddique, M.D., the Les Turner ALS Foundation/Herbert C. Wenske Professor of the Davee Department of Neurology and Clinical Neurosciences at Northwestern's Feinberg School and a neurologist at Northwestern Memorial Hospital. "This gives us a clear target to develop drug therapies to try to fix this problem. It strengthens our belief that this broken system is at the heart of ALS."

The new "bad player" is called sequestosome1. The previously identified mutated gene is ubiquilin2. Because these two genes aren't doing their jobs to recycle damaged proteins, those proteins as well as sequestosome1 and ubiquilin2 -- accumulate abnormally in the motor neurons in the spinal cord and cortical and hippocampal neurons in the brain. The protein accumulations resemble twisted skeins of yarn -- characteristic of ALS -- and cause the degeneration of the neurons.

In the new study, sequestosome1 genetic mutations were identified in 546 ALS patients; 340 with an inherited form of the disease, called familial, and 206 with a non-inherited form of the disease, called spora
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Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University
Source:Eurekalert

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