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:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and fastest ... to open a flagship location in Covington, LA at 401 N. U.S. Highway 190, ... next to Office Depot in the Holiday Square shopping center. Its location allows it ...
(Date:10/12/2017)... Fla. (PRWEB) , ... October 12, 2017 , ... IsoComforter, ... therapy products, announced today the introduction of an innovative new design of the shoulder ... pad so you get maximum comfort while controlling your pain while using cold therapy. ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... leader in post-acute health care, have expanded their existing home health joint venture ... , AccentCare has been operating a joint venture home health company with Asante, ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... Mohebi Hair Restoration, has recently contributed a medical article to the newly revamped ... cosmetictown.com. Dr. Mohebi’s article spotlights the hair transplant procedure known as Follicular ...
(Date:10/12/2017)... ... October 12, 2017 , ... Leading pediatric oncology experts at ... for the 49th Congress of the International Society of Paediatric Oncology (SIOP) ... Center for Cancer and Blood Disorders at Children’s National, and Stephen P. ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)...  According to the Centers for Disease Control and Prevention (CDC), ... Urgent Care is helping communities across Massachusetts , ... offering no-cost* flu shots through the end of the month. ... regulations. ... a flu shot is by the end of October, according to the ...
(Date:10/2/2017)... , Oct. 2, 2017 Halo Labs announces the European ... system called the HORIZON at MIBio 2017 in Cambridge, ... and visible particulate matter in biopharmaceutical samples with unprecedented speed and ... the novel technique Backgrounded Membrane Imaging. ... The HORIZON subvisible particle analysis system ...
(Date:9/27/2017)... , Sept. 27, 2017  DarioHealth Corp. (NASDAQ: DRIO), a leading ... announced that its MyDario product is expected to appear on The Dr. ... The Dr. Oz Show airs in your area: http://www.doctoroz.com/page/where-watch-dr-oz-show ... The nine-time Emmy award-winning, The Dr. Oz Show ... The segment ...
Breaking Medicine Technology: