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Genomic transposable elements modify the progression of Parkinson’s disease

WASHINGTON – November 8, 2022 – (Newswire.com)

A recently published article in Experimental Biology and Medicine (Volume 247, Issue 18, September, 2022) improves our understanding of genomic transposable elements and Parkinson’s disease. The study, led by Dr. Sulev Koks, head of Genetic Epidemiology Research at Perron Institute for Neurological and Translational Science and the Centre for Molecular Medicine and Innovative Therapeutics at Murdoch University (Australia), and Dr. John Quinn, chair of Neurobiology in the department of Pharmacology and Therapeutics at the University of Liverpool (United Kingdom), describes how transposable elements were associated with Parkinson’s subtypes and impact disease trajectory.

Transposable elements make up more than 70% of the human genome, but until recently, they have been considered as ‘junk’ DNA without any meaningful function. These elements have been largely ignored in most genetic studies and could therefore contribute to the currently unknown genetic factors that influence disease development. Prior studies by Koks and colleagues have shown that these elements have a significant regulatory role in the genome. They regulate the expression of many genes, orchestrate complex genetic activation where multiple genes are needed for a complex response, and a growing body of evidence suggests that these elements have a major pathogenetic effect, with several elements shown to cause disease.

This study, led by Dr. Koks, analyzed the variation of transposable elements and their impact on different trajectories of Parkinson’s disease. They used patient data from the Parkinson’s Progression Markers Initiative, and five-year follow-up data from Parkinson’s patients who also had whole genome sequencing data available. This allowed them to develop a comprehensive genomic screen for the transposable elements in these patients. Koks et al found that transposable elements were associated with Parkinson’s subtypes and disease trajectory. Some transposable elements predicted faster progression of the disease, with very fast deterioration of motor or cognitive functions. The effect of transposable elements wasn’t unidirectional. Depending on their type and position in the genome, these elements had a negative or positive effect. Some elements were associated with a strong and clinically meaningful change in functional Parkinson’s scores. At the same time, some transposable elements were protective and associated with a slower disease progression suggesting a slowing of neuronal loss and neurodegeneration.

Dr. Koks said: “Transposable elements are part of the genome which is known as the ‘dark genome.'” He continued: “Our study showed that the dark genome may have a much more significant impact on the pathophysiology of complex disease than previously estimated. The elements inside the dark genome could enhance or slow the progression of Parkinson’s disease and therefore open up new opportunities for precision medicine.” Dr. Quinn added, “Our body of work over a decade highlights the importance of targeting these elements for therapeutic intervention in the progression of neurodegenerative diseases which is the subject of our current work not only in Parkinson’s Disease but also Motor Neurone Disease. This could include repositioning of drugs from other disease areas in which these elements are implicated in disease progression.”

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said “This fascinating study by Koks and his colleagues demonstrates that the presence or absence of transposable elements controls the progressions trajectory of Parkinson’s Disease. It further underscores the importance of rigorous analysis of these genomic elements is essential for considering therapeutic opportunities.”

Experimental Biology and Medicine is a global journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal, please visit http://ebm.sagepub.com.

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Contact Information:

Benjamin Zimmer

bzimmer@sebm.org

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Genomic transposable elements modify the progression of Parkinson’s disease

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