A second 'bad' gene is linked to damaged cell buildup, paralysis in ALS

November 21, 2011, Northwestern University

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 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 -- a new loafing worker -- in the same recycling pathway. The finding is reported in .

"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 at Northwestern Memorial Hospital. "This gives us a clear to develop 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 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 sporadic.

About 90 percent of ALS is sporadic and 10 percent is familial. To date, mutations in about 10 genes, several of which were discovered at Northwestern, including SOD1 and ALSIN, account for about 30 percent of classic familial ALS, noted Faisal Fecto, M.D., study lead author and a PhD candidate in neuroscience at Feinberg.

ALS affects an estimated 350,000 people worldwide, including children and adults, with about 50 percent of people dying within three years of its onset. In the motor disease, people progressively lose muscle strength until they become paralyzed and can no longer move, speak, swallow and breathe. ALS/dementia targets the frontal and temporal lobes of the brain, affecting patients' judgment, the ability to understand language and to perform basic tasks like planning what to wear or organizing their day.

The discovery of the breakdown in recycling may also have a wider role in other neurodegenerative diseases, particularly the dementias. These include Alzheimer's disease and frontotemporal dementia as well as Parkinson's disease, all of which are characterized by aggregations of proteins, Siddique said. The removal of damaged or misfolded proteins is critical for optimal cell functioning, he noted.

Explore further: Major breakthrough as researchers discover common cause of all forms of amyotrophic lateral sclerosis

Related Stories

Major breakthrough as researchers discover common cause of all forms of amyotrophic lateral sclerosis

August 21, 2011
The underlying disease process of amyotrophic lateral sclerosis (ALS and Lou Gehrig's disease), a fatal neurodegenerative disease that paralyzes its victims, has long eluded scientists and prevented development of effective ...

Recommended for you

Discovery of the 'pioneer' that opens the genome

January 23, 2018
Our genome contains all the information necessary to form a complete human being. This information, encoded in the genome's DNA, stretches over one to two metres long but still manages to squeeze into a cell about 100 times ...

Researchers identify gene responsible for mesenchymal stem cells' stem-ness'

January 22, 2018
Many doctors, researchers and patients are eager to take advantage of the promise of stem cell therapies to heal damaged tissues and replace dysfunctional cells. Hundreds of ongoing clinical trials are currently delivering ...

Genes contribute to biological motion perception and its covariation with autistic traits

January 22, 2018
Humans can readily perceive and recognize the movements of a living creature, based solely on a few point-lights tracking the motion of the major joints. Such exquisite sensitivity to biological motion (BM) signals is essential ...

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.