02:06pm Monday 14 October 2019

New gene mutation responsible for neurodegenerative disorder

The findings, published in prestigious EMBO (European Molecular Biology Organisation) Journal this week, could also help in the mission to find anti-cancer drugs.

Dr Ivan Ahel, from Cancer Research UK’s Paterson Institute based at The University of Manchester, led the study which has unearthed the function of the gene called c6orf130, mutation of which leads to a severe progressive neurodegenerative disease and seizure disorder.

The mutation of c6orf130 causes a defect in an enzyme which removes small chemical tags called ADP-ribose from proteins, the study shows. As the timely removal of the ADP-ribose tags in cellular proteins is required for normal cell growth and repair, the researchers hope that this enzyme could become an important target for new drugs aimed at inhibiting growth of cancer cells.

In the past scientists have been able to design anticancer drugs to prevent attachment of ADP-ribose to proteins(protein ADP-ribosylation) by inhibiting enzymes that make this modification (called PARPs). But a reversing enzyme which could completely uncouple these small molecules (ADP-ribose) has remained elusive – dispute this cellular activity been known to exist for more than 30 years. The new enzyme has been named the TARG1 (for terminal ADP-ribose glycohydrolase protein).
Dr Ahel said: “This is a very important study. The discovery of an enzyme which can reverse the modification of proteins modified by PARPs is very exciting and with further research could have implications to anti cancer drugs and neurodegenerative disorders.”

The study was made up of experts from the US, Germany and St George’s, University of London and involved a series of clinical, biochemical and structural studies to come up with the findings. 

The C6orf130 gene was identified for a group of neurodegenerative disorders by geneticists at the Human Genetics Research Centre at St George’s, University of London, led by Dr Reza Sharifi. He said: “We will now carry out further investigations to discover the exact cellular process involved which suggests a new mechanism may operate in a wider range of neurodegenerative disorders – the genetics of which is still very poorly understood.”

Dr Sharifi added: “Much of our understanding of how proteins work is identified by looking at the disease. It’s been very exciting to work with researchers from different disciplines to further our understanding of these enzymes.”

Notes for editors

To view the journal, article please click here: http://www.nature.com/emboj/journal/vaop/ncurrent/full/emboj201351a.html


For further information, please contact:

Alison Barbuti

Media Relations Officer

Faculty of Medical and Human Sciences

0161 275 8383

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