Scientists Identify New Cause for Inherited Neurodegenerative Diseases

New research led by neuroscience experts from the University of Plymouth, Fudan University, and Tsinghua University may have found the cause of genetic mutations that can cause rare conditions, such as Huntington disease.

Neurodegenerative disease concept illustration with neural networks | Image credit: Picture-waterfall - stock.adobe.com

The previous known cause of neurodegenerative diseases and spinocerebellar ataxias (SCAs) was cytosine-adenine-guanine (CAG). When CAG is expanded it repeats within a gene and leads to a polyglutamine (polyQ) tract in a protein, which can be passed down to offspring.

Huntington disease is a rare, inherited disease that causes a progressive breakdown of nerve cells in the brain. This disease gets worse over time and can affect movement, cognition, and mental health.

The study notes that in the recent discoveries, scientists found that ribonucleic acid (RNA) can produce levels of toxicity that can cause damage to brain in the highlighted diseases.

“The research has revealed that expanded CAG repeat RNA can form RNA aggregates in the cytoplasm through a process called liquid-liquid phase separation and gelation. This reduces global protein synthesis and leads to neurotoxicity and neurodegeneration,” said the study authors.

The study authors note that this finding provides more knowledge to researchers working to recognize the cause of inherited conditions. The scientists are planning to further this knowledge by conducting a second study to focus on the expanded CAG repeats and RNA aggregate toxicity in patients suffering with these conditions.

"Conditions such as Huntington's disease currently have few treatments and no known cure. If we are to make the significant steps needed to directly benefit patients and their families, we need to fully understand the nature of the conditions we are dealing with,” said Shouqing Lou, PhD, Professor of Neurobiology at the University of Plymouth. “This study marks a real step forward in what we know about the causes of Huntington's disease and other neurodegenerative conditions. It provides us with new mechanistic insights into diseases such as HD and SCAs that we can potentially use in the future to develop more effective ways of treating these conditions."

The findings suggest that the recent discovery of CAG repeat RNA aggregate could aid further research on the cause of Huntington disease and other inherited conditions.

Reference

Study uncovers potential new source of genetic mutations that cause neurodegenerative disease. Science Daily. News release. August 17,2023. Accessed August 23, 2023. https://www.sciencedaily.com/releases/2023/08/230817163900.htm.