Featured Research

from universities, journals, and other organizations

More Genes For Lou Gehrig's Disease Identified

Date:
April 8, 2008
Source:
University of Pennsylvania School of Medicine
Summary:
In recent months a spate of mutations have been found in a disease protein called TDP-43 that is implicated in two neurodegenerative disorders: amyotrophic lateral sclerosis, also called Lou Gehrig's disease, and certain types of frontotemporal dementia. These mutations could potentially become candidates for drug targets. Recently, scientists have found two more mutations.

In recent months a spate of mutations have been found in a disease protein called TDP-43 that is implicated in two neurodegenerative disorders: amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, and certain types of frontotemporal dementia (FTD). These mutations could potentially become candidates for drug targets.

Recently, colleagues at the University of Pennsylvania School of Medicine and Veterans Affairs in Seattle, WA have found two more mutations. They published their findings online in advance of print publication in the May issue of The Lancet Neurology.

"Now we have a direct link between the genetics and the clinical pathology of these diseases," says co-author Vivianna M. Van Deerlin, MD, PhD, Assistant Professor of Pathology and Laboratory Medicine at Penn. "This solves the question of whether TDP-43 is involved in the disease itself or a just a byproduct of it."

"Put this all together and it becomes completely convincing that there are mutations in this gene that causes some forms of ALS," says co-author Gerard D. Schellenberg, PhD, Associate Director for Research, Veterans Affairs Puget Sound Health Care System, in Seattle, WA

Essentially, these mutations are hard evidence that TDP-43 is critical for the disease process. In some cases the accumulation of TDP-43 may initiate disease; in others, it might be a downstream player in the onset of pathology.

In late 2006, Virginia Lee, PhD and John Trojanowski, MD, PhD at the Center for Neurodegenerative Disease Research at Penn found that TDP-43 accumulated abnormally in post-mortem brain tissue from individuals diagnosed with either disease. The misfolded, disease protein was recovered from only affected central nervous system regions, which include the hippocampus, neocortex, and spinal cord. TDP-43 is normally involved in RNA and DNA processing, among other cellular tasks.

The research team surveyed 259 individuals with either ALS or ALS combined with FTD and brains with pathological TDP-43 protein present and determined the DNA sequence of the gene for TDP-43 and compared it to the normal TDP-43 sequence in people without these diseases.

"By doing this, we found two families in which a mutation was present and showed that the mutated gene tracked with the disease," says Van Deerlin. "Within the same family, all people tested who have the disease carry the mutated form of TDP-43 and it was absent in the unaffected people tested."

With this, the research group then asked: Do we see this same change in people that don't have the disease outside of the families as controls? The group tested 747 Caucasian and 380 Chinese elderly people without the disease and didn't find the mutated form of TDP-43 in any of them.

"What makes our paper completely distinctive is that we have post-mortem brain tissue from some individuals in one of the ALS families," says Schellenberg. "We showed that people with a mutated form of TDP-43 actually have TDP-43 deposited in their brain."

The researchers stress the implications beyond ALS and FTD: TDP-43 shows up in a variety of diseases, for example 20 percent of Alzheimer's cases. "These findings are not just important to ALS, it's every disease where there is a pathological form of TDP-43," notes Schellenberg. The next step will be to gain a better understanding of how the mutation in TDP-43 causes disease.

This work was funded by the National Institutes of Health, the Department of Veterans Affairs, the Friedrich-Baur Stiftung, the US Public Health Service, the ALS Association, and a fellowship from Fundaciσ 'la Caixa', Spain.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of Pennsylvania School of Medicine. "More Genes For Lou Gehrig's Disease Identified." ScienceDaily. ScienceDaily, 8 April 2008. <www.sciencedaily.com/releases/2008/04/080407160234.htm>.
University of Pennsylvania School of Medicine. (2008, April 8). More Genes For Lou Gehrig's Disease Identified. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2008/04/080407160234.htm
University of Pennsylvania School of Medicine. "More Genes For Lou Gehrig's Disease Identified." ScienceDaily. www.sciencedaily.com/releases/2008/04/080407160234.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) — West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) — A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) — Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) — Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
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