To Live or to Die: Scientists Unravel How DNA Repair Guards us Against Motor Neuron Disease

Dementia and Motor neuron disease (MND) are among the most common neurodegenerative disorders in Egypt, affecting people in the middle of their active life.

The most common genetic cause of these devastating diseases is an expansion in a gene called C9orf72. The normal C9orf72 gene contains a region where a series of six DNA nucleotides – the building blocks of our DNA - occurs once or repeated multiple times. When this series of nucleotides is excessively repeated, neurons dies!

Why and how this expansion kills neurons is unknown.

Zewail City PhD student Waheba El-Sayed in collaboration with a multidisciplinary team led by the director of the center of Genomics at Zewail City, Dr Sherif El-Khamisy have now worked out the answer to this question, published this week in the world leading journal, Nature Neuroscience.

During the process of reading the instructions written in our DNA to make useful proteins, an intermediate form of genetic material is formed, called RNA. The RNA produced from these expansions got special properties that make the DNA - where all important cellular information is stored -  vulnerable to breakage. These genomic breaks are a real threat to cells since they interfere with all cellular activities and can cause cell death.

 

Luckily, our cells got repair toolkits specially designed to fix these breaks as and when they arise. Sadly however, the products of the expansion in patients with dementia and ALS results in protein and RNA aggregates that suck specific components of our precious repair toolkits – in a process called autophagy - making it even more difficult for cells to carry on, and they eventually die. The team was able to prevent neuronal cell death by modulating certain DNA repair toolkits using gene therapy approaches.

Publisher:

Nature Neuroscience- It is the top and the world-leading journal in Neuroscience with impact factor 16.874

Authors:

Callum Walker1,2,3¶, Saul Herranz-Martin2¶, Evangelia Karyka1,2.3, Chunyan Liao3, Katherine Lewis2, Waheba Elsayed4, Vera Lukashchuk2, Shih-Chieh Chiang3, Swagat Ray3, Padraig J. Mulcahy2, Mateusz Jurga3, Ioannis Tsagakis2,Tommaso Iannitti2,Jayanth Chandran2,Ian Coldicott2, Kurt J De Vos2, Mohamed K. Hassan4, Adrian Higginbottom2, Pamela J. Shaw2, Guillaume M. Hautbergue2, Mimoun Azzouz1,2, Sherif F. El-Khamisy1,3,4*

 

Institutions Order:

1SITraN and Krebs Institutes, Neurodegeneration and Genome Stability Group, University of Sheffield, UK

2Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, S10 2HQ, Sheffield, UK

3Krebs and Sheffield Institutes for Nucleic Acids, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, S10 2TN, Sheffield, UK

4Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt.


* Lead and corresponding author

Benefit this research provides to society and layman

  1. Potential cure for Dementia
  2. Potential cure for motor neuron disease (ALS)
  3. Potential cure for other related neurological disease such as Alzhemier’s and Parkinson’s
  4. Provides the lay with precautions and guidelines for what to do to prevent neurological disease.

The first link between two recent Nobel Prize discoveries: Autophagy (2016) and DNA Repair (2015).