The ALS Association

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Carrie Munk
The ALS Association
(571) 319-3047



ALS Gene Mutation Disrupts Critical Neuronal Transport Process

Washington, D.C. (February 5, 2014)—In work supported by The ALS Association, researchers have shown that the ALS-associated protein TDP-43 is critical for transport within neurons. The study was published in the journal Neuron.

ALS (amyotrophic lateral sclerosis), also referred to as Lou Gehrig’s Disease, is a progressive neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease. 

Virtually all people with ALS have abnormal aggregates of protein in their dying motor neurons that contain TDP-43 protein. How or whether these aggregates contribute to disease is unknown. In addition, mutations in the TDP-43 gene cause a small number of ALS cases and how the mutation causes disease is also unknown.

To learn more about the normal function of TDP-43 and to understand the disease process better, Association-supported scientist J. Paul Taylor, Ph.D., of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues examined the movement of the protein using special dyes. The protein binds to thousands of different messenger RNA molecules (mRNAs), the “working copies” of genes used to make proteins.

The authors found that normal TDP-43 is incorporated into so-called ribonucleoprotein  granules, which are transported between the cell nucleus and the tip of the axon, the long extension connecting one neuron to another. The granules were transported in both directions—from the nucleus down the axon and back up the axon to the nucleus. But granules containing mutant TDP-43 protein were less likely to be moved away from the nucleus and more likely to be moved toward it. This change in average motion was seen in several disease models, including in neurons derived from ALS patient skin cells.

“Axonal transport is critical for the function of neurons,” said Lucie Bruijn, Ph.D., Chief Scientist for The Association, “and these results tell us that TDP-43 mutation has an important effect on that transport. How this alteration in transport contributes to disease is not yet known, but it provides essential new information we can use to better understand the consequences of the TDP-43 mutation. It also may help us understand the significance of the protein aggregates seen in virtually all people with ALS. That may lead to therapies targeted at these structures.”

About The ALS Association
The ALS Association is the only national non-profit organization fighting Lou Gehrig’s Disease on every front.  By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure.  For more information about The ALS Association, visit our website at

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