Neurodegeneration Linked To ADP-Ribose

In European news, EMBO.org (European Molecular Biology Organization) reports that researchers have identified an enzyme that removes ADP-ribose modifications from proteins by studying a genetic mutation that causes neurodegenerative disease in humans. These findings, suggest that not only addition but also removal of ADP-ribose from proteins is essential for normal cell function. Poly ADP-ribose or PARP chains play key roles in the repair of cellular DNA damage, and in the control of gene expression and cell death. Pharmacological drugs called PARP inhibitors prevent the addition of ADP-ribose or their polymers to proteins. Several of these drugs are undergoing clinical trials for the treatment of different types of cancers.

A breakthrough in the study came when collaborators from the National Institutes of Health, USA and Ludwig Maximilians University, Munich teamed up with clinical geneticists at the Human Genetics Research Center at St. George's University of London lead by Reza Sharifi. She stated,

“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.”

She continued to explain that the product of this gene, 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 rapid increase of cells and response to DNA damage.

The full research article can be found at The EMBO Journal.

If you read further into the linked articles it talks about how researchers found a gene that was mutated in a family that had several cases of severe progressive neurodegenerative and seizure disorder. The findings revealed that the attaching and removing chains of ADP-ribose to proteins are important to cell survivability and DNA repair. I find it simply amazing that they can analyze patients with a family history of neurodegeneration to gain a better understanding of this mechanism and perhaps give them a better understanding of what is happening to them and eventually, I believe, how to correct it. They are getting ever closer to finding out the exact enzyme(s) that may be responsible for it.