The ALS Association

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Carrie Munk
The ALS Association
(571) 319-3047



New Evidence Supports Nuclear Transport Disruption as a Key ALS Pathway

Washington, D.C., (January 15, 2016) — Researchers from the Max Planck Institute of Biochemistry in Martinsried, Germany demonstrated that protein aggregates, like those found in the neurons of most people with ALS, are toxic when they occur in a cell’s cytoplasm, not its nucleus. The study was published in the Jan. 8, 2016 issue of the journal Science titled, “Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA.” These cytoplasmic aggregates interrupted transport of materials to and from the nucleus. The findings add to earlier publications highlighting the potential of disrupted nuclear transport as a disease pathway in ALS and may lead to better targeting of therapy.

In the study, researchers introduced artificial proteins that carried localization sequences, akin to zip codes, that restricted them to either the cell’s nucleus or its surrounding cytoplasm. The proteins were designed to form aggregates, clumps of protein that are thought to interfere with cell function. Protein aggregates are a common feature in numerous neurodegenerative diseases, including ALS, Alzheimer’s disease, Parkinson’s disease, among others. The researchers found that only the cytoplasmic aggregates were toxic.

The team also found that cytoplasmic aggregates disrupted transport of materials across the nuclear membrane. Disrupted nuclear transport has recently emerged as a potentially major disease pathway in ALS, following work by ALS Association-funded researchers.

“The results in this study strengthen the case that interference with nuclear transport is a key element of the disease process in ALS,” said Association Chief Scientist Lucie Bruijn, Ph.D., M.B.A. “Treatments that are aimed at preventing or reducing cytoplasmic aggregation of ALS-related proteins, including TDP-43, will be important to explore for their potential in ALS.”

About ALS
ALS is a progressive neurodegenerative disease that affects 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. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration (FDA) modestly extends survival.

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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