Navigation Links
More genes for Lou Gehrig's disease identified, according to Penn researchers
Date:4/7/2008

PHILADELPHIA - 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 Gehrigs 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 dont have the disease outside of the families as controls? The group tested 747 Caucasian and 380 Chinese elderly people without the disease and didnt 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 Alzheimers cases. These findings are not just important to ALS, its 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.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Pathway links inflammation, angiogenesis and breast cancer
2. Traffic Fumes Plus Genes Boosts Kids Asthma Risk
3. New Database to Help Speed Search for Bipolar Disorder Genes
4. Is Perfect Pitch All in the Genes?
5. Discovery suggests location of genes for breast density, a strong risk factor for breast cancer
6. Genes Boost Risk for Rheumatoid Arthritis, Lupus
7. The genes involved in rheumatoid arthritis identified
8. If you think cancer genes are simple, you dont know JAK
9. Test for lung cancer looks for discomforting quiet among protective genes
10. Hushed Genes Might Mean Higher Lung Cancer Risk
11. EURYI project to understand how the brain wires during embryogenesis
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... 2016 , ... "FCPX editors can now reveal their media with growing colorful ... Christina Austin - CEO of Pixel Film Studios. , ProSlice Color brings the ... can now reveal the media of their split screens with growing colorful panels. , ...
(Date:6/26/2016)... ... ... Quality metrics are proliferating in cancer care, and are derived from many ... the beholder, according to experts who offered insights and commentary in the current issue ... the full issue, click here . , For the American Society of Clinical ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are confused ... endometriosis. These women need a treatment plan to not only alleviate symptoms and ... help for preservation of fertility and ultimately achieving a pregnancy. The specialists at ...
(Date:6/25/2016)... ... 25, 2016 , ... First Choice Emergency Room , the largest network ... the Medical Director of its new Mesquite-Samuell Farm facility. , “We are pleased ... location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... A recent ... that most people are unfamiliar with. The article goes on to state that individuals ... also many of these less common operations such as calf and cheek reduction. The ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on ... today announced that patient enrollment in its ongoing ... Duchenne) has exceeded 50% of its 24-patient target. ... in the third quarter of 2016, and to ...
(Date:6/23/2016)... , June 23, 2016 , ... on Thursday, July 7, 2016 , , , , LOCATION: ... , , , , EXPERT PANELISTS:  , , , ... Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar and ... The global pharmaceutical industry is witnessing an exceptional era. ...
(Date:6/23/2016)... LONDON , June 23, 2016 ... environments  Oticon , industry leaders in ... the launch of Oticon Opn ™, the world,s ... world of possibilities for IoT devices.      ... Opn, Oticon introduces a number of ,world firsts,: ...
Breaking Medicine Technology: