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:12/5/2016)... (PRWEB) , ... December 05, 2016 , ... ... announces today that they have teamed up with The American College of Surgeons ... the ACS’s Committee on Trauma, the “Bleeding Control Basic” course is a pilot ...
(Date:12/4/2016)... Fl (PRWEB) , ... December 02, 2016 , ... ... that will give patients better access to nutraceuticals and help doctors more efficiently ... EMR patient portal and practice management software platform for Integrative and Functional Medicine. ...
(Date:12/4/2016)... ... December 03, 2016 , ... ... transitions and many more tools allowing FCPX editors to create professional looking video ... Studios. , Perfect Harmony contains a beautifully designed 3D environment for placing ...
(Date:12/4/2016)... ... December 03, 2016 , ... ... at the 2016 Anti-Aging & Beauty Awards at The Aesthetic & ... & Anti-Aging Medicine European Congress (AMEC) brings together the industry’s leading scientific ...
(Date:12/4/2016)... (PRWEB) , ... December 04, 2016 , ... ... presets that have new attractive animation styles with unique displacement design elements," said ... 30 pre-animated lower third designs. Choose from a variety of design styles that ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... 2, 2016 Quantum Radiology,s Mobile Breast Center ... interpretation directly to women at the workplace, thereby maximizing ... as Delta Air Lines and SunTrust Bank, and community ... component of wellness initiatives. "I think it,s ... enables them to have a mammogram without taking a ...
(Date:12/2/2016)... ALEXANDRIA, Va. , Dec. 2, 2016 /PRNewswire-USNewswire/ ... year by the Academy of Managed Care Pharmacy ... care organizations can better address the opioid addiction ... Medication Assisted Therapies (MAT). ATAG,s newly ... in Improving Access to Naloxone," addresses many issues ...
(Date:12/2/2016)... 2, 2016 CVS Health Corporation (NYSE: ... in New York City on Thursday, December 15, 2016, beginning at 8:00 a.m. ... will provide an in-depth review of the company,s strategies ... company will also discuss 2017 earnings guidance during the ... the event will be broadcast simultaneously on the Investor ...
Breaking Medicine Technology: