‘Junk DNA’ May Provide New Treatment for Neurological Disorders

For many years, geneticists only focused on the portions of the human genome that code for protein, but those sequences only represent about two percent of the human genome. The rest of the genome is often made up of highly repetitive sequences that are difficult to amplify and, thus, difficult to study using traditional laboratory techniques. As such, it was dismissed as ‘junk DNA‘ and mostly ignored for several decades.  

However, a new study led by scientists at the University of Sheffield’s Neuroscience and Healthy Life Span Institutes showed that junk DNA is much more vulnerable to breaks from oxidative genomic damage than previously thought. The findings are published in the journal Nature and may provide vital implications for treating neurological disorders. 

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Understanding the Oxidative Damage Repair Mechanism

The study shows that junk DNA is extremely susceptible to breaks caused by oxidative stress on the genome. The researchers also uncovered how those oxidative stress-related breaks are created and repaired.  

Oxidative stress is a natural byproduct of many cellular processes, and external factors such as the environment or dietary intake can easily affect it. In the long term, oxidative stress can cause damage to the body’s cells, proteins, and DNA, accelerating the aging process and contributing to the development of neurological diseases such as dementia. 

In the report, scientists identified the role of NuMA in protecting gene promoters from damage caused by oxidative stress. NuMA, which is encoded by the NUMA1 (nuclear mitotic apparatus protein) gene, is a structural protein related to lamins that localize at spindle poles during mitosis. It is often found within 100 base pairs of transcription start sites, where cellular machinery starts transcribing active genes into RNA molecules. When NuMA levels are low, oxidative stress disrupts gene promoters.  

Potential for a Variety of Indications

Future research will focus on working with patients to investigate the pathogenic variants linked to this pathway. Furthermore, the team hopes to collaborate with pharmaceutical companies to speed up the detection of disease biomarkers and allow for earlier intervention to help prevent the onset or progression of neurological disorders such as Alzheimer’s and MND, especially in those with the relevant gene.   

Other than its potential in neurological disease treatment, the researchers believe that inhibiting the activity of a key component of the pathway, NuMA, may help stop the survival of nondividing dormant cancer cells, which are difficult to treat. 

Author

Nai Ye Yeat