Navigation Links
Hereditary neurodegeneration linked to ADP-ribose modification
Date:3/12/2013

HEIDELBERG, 12 March 2013 Attaching chains of the small molecule ADP-ribose to proteins is important for a cell's survival and the repair of DNA damage, making this process a promising target for the development of new cancer drugs. Researchers have now identified a much sought after enzyme that removes such ADP-ribose modifications from proteins by studying a genetic mutation that causes neurodegenerative disease in humans. These findings, published today in The EMBO Journal, suggest that not only addition but also removal of ADP-ribose from proteins is essential for normal cell function.

Poly(ADP-ribose) chains have key roles in the repair of cellular DNA damage, as well as in the control of gene expression and cell death. Pharmacological drugs called PARP inhibitors prevent the addition of ADP-ribose or ADP-ribose polymers to proteins. Several of these drugs are undergoing clinical trials for the treatment of different types of cancers.

EMBO Young Investigator Ivan Ahel, a group leader at the Paterson Institute for Cancer Research at the University of Manchester, has been studying the underlying molecular processes, including an enzyme that shortens such chains piece by piece. "An enzyme that could completely uncouple ADP-ribose from proteins has remained elusive, even though such a cellular activity has been known to exist for more than 30 years," commented Ahel. "Our approach has been to combine clinical, biochemical and structural studies to see if we could pin point this enzyme activity in humans."

The eventual breakthrough came when Ahel and his collaborators Scott Williams (National Institutes of Health, USA), Gyula Timinszky and Andreas Ladurner (both from Ludwig Maximilians University Munich) teamed up with a group of clinical geneticists lead by Reza Sharifi at the Human Genetics Research Center at St George's University of London. "By studying genetic mutations in a group of patients with severe neurodegenerative disease, we found a gene that was mutated in a family that had several cases of severe progressive neurodegenerative and seizure disorder," remarked Sharifi. The product of this gene, which was named TARG1 (for terminal ADP-ribose protein glycohydrolase), exhibited the long-sought-after enzyme activity that fully removes ADP-ribose from proteins, and was further required for the proliferation of cells and response to DNA damage.

The researchers note that further work is needed to investigate the exact cellular processes where TARG exerts its functions, and to understand in more detail why mutation of this gene causes neurodegenerative disease. "Our discovery suggests a new pathogenic mechanism that may operate in a wider range of neurodegenerative disorders, the genetics of which generally remain very poorly understood," concluded Sharifi.


'/>"/>

Contact: Barry Whyte
barry.whyte@embo.org
49-622-188-91108
European Molecular Biology Organization
Source:Eurekalert

Related medicine news :

1. A scanner for hereditary defects
2. Developed new method to diagnose hereditary breast and ovarian cancer
3. The prevention of hereditary breast and ovarian cancer by PGD is feasible
4. Stroke risk in elderly treated with antipsychotics is newly linked to specific drug actions
5. Study finds fat and bone mass are genetically linked
6. Daily Aspirin Linked to Lower Risk for Deadly Skin Cancer in Women
7. Neck injuries linked to high costs for patients and spouses, reports study in Spine
8. Vision Loss, Depression May Be Linked, Study Finds
9. Lack of aspirin before angioplasty linked with higher mortality
10. Weight loss linked to higher risk with implanted defibrillators
11. Secondhand Smoke Linked to Early Heart Disease, Study Finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/2/2016)... ... May 02, 2016 , ... It has just been announced ... speaker for five events throughout the month of May. , Uldrich is the author ... news outlets. He also frequently appears on the Science Channel’s FutureScape and Discovery Channel’s ...
(Date:5/2/2016)... ... May 02, 2016 , ... ProElectric Cartoon is a package of 30 hand-drawn ... from a variety of electric styles including zap, sizzles, and more. Easily alter the ... blur, three dimensional rotation, and much more. ProElectric Cartoon’s simplistic style makes it the ...
(Date:5/2/2016)... ... May 02, 2016 , ... As directed by its board ... (HAP) issues its full support to allow certified nurse practitioners (CNP) to practice to ... have worked under such supervision for three years and 3,600 hours. , In addition, ...
(Date:5/2/2016)... ... May 02, 2016 , ... ... traditions of innovation by partnering with college students at University of Colorado in ... CU-Boulder senior level advertising campaigns class in the School of Journalism, who selected ...
(Date:5/2/2016)... ... ... Eating Recovery Center’s Insight Behavioral Health Center (ERC Insight) , a ... eating disorder program under a new name: Eating Recovery Center, Chicago (ERC Chicago). ERC ... , To celebrate, ERC Chicago will host a ribbon-cutting ceremony and open house on ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... N.J. , April 28, 2016   Acsis ... today announced that leading IT market research and advisory ... " in the IDC MarketScape: Worldwide Pharmaceutical Track and ... 2016).  The report provides an assessment of the capabilities ... track and trace software market. Logo - ...
(Date:4/28/2016)... , April 28, 2016 ... H1 2016" is a report that provides an ... strengthen R&D pipelines by identifying new targets and ... Company Profiles discussed in this H1 2016 ... Riunite Srl, AbbVie Inc., Abiogen Pharma S.p.A., Ablynx ...
(Date:4/27/2016)... , le 27 Avril 2016 ... d,affaires a progressé de +5% sur le trimestre, ... récurrentes de consommables  Croissance de +16% ... Mauna Kea Technologies (Euronext : MKEA, ... d,endomicroscopie confocale laser, annonce aujourd,hui son chiffre d,affaires ...
Breaking Medicine Technology: