Featured Research

from universities, journals, and other organizations

New culprit found in Lou Gehrig's disease

Date:
November 22, 2011
Source:
Northwestern University
Summary:
Following a breakthrough identifying a common converging point for all forms of Lou Gehrig's disease, a new finding from the same scientists shines more light on the broken recycling pathway of the brain and spinal cord cells, which leads to the paralysis of ALS. The new study reveals a second faulty gene in the same pathway, offering a clear target for drug therapy.

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 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 protein 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.

The study was supported by the National Institute of Neurological Disorders and Stroke, the Les Turner ALS Foundation, the Herbert and Florence C. Wenske Foundation and other sources.


Story Source:

The above story is based on materials provided by Northwestern University. The original article was written by Marla Paul. Note: Materials may be edited for content and length.


Journal Reference:

  1. F. Fecto, J. Yan, S. P. Vemula, E. Liu, Y. Yang, W. Chen, J. G. Zheng, Y. Shi, N. Siddique, H. Arrat, S. Donkervoort, S. Ajroud-Driss, R. L. Sufit, S. L. Heller, H.-X. Deng, T. Siddique. SQSTM1 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis. Archives of Neurology, 2011; 68 (11): 1440 DOI: 10.1001/archneurol.2011.250

Cite This Page:

Northwestern University. "New culprit found in Lou Gehrig's disease." ScienceDaily. ScienceDaily, 22 November 2011. <www.sciencedaily.com/releases/2011/11/111121194039.htm>.
Northwestern University. (2011, November 22). New culprit found in Lou Gehrig's disease. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2011/11/111121194039.htm
Northwestern University. "New culprit found in Lou Gehrig's disease." ScienceDaily. www.sciencedaily.com/releases/2011/11/111121194039.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins