Scientists have discovered an additional potential cause of the genetic mutations that result in rare conditions such as Huntington's disease (HD).
The neurodegenerative diseases, which also include most spinocerebellar ataxias (SCAs), are known to be caused by an expansion in the CAG (cytosine-adenine-guanine) repeats within a gene that in turn leads to an expanded polyglutamine (polyQ) tract in a protein.
Such diseases are inherited, given that the expansion of CAG repeats in a gene can be passed down the generations.
Previously, it had been thought the damage in these genetic diseases was caused solely by increased protein aggregate toxicity.
However, a new study has found an additional source - ribonucleic acid (RNA) - can generate the levels of toxicity to cause damage to the brain in these diseases.
Published in Nature Chemical Biology, 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.
The study is part of an ongoing international collaboration between experts in neuroscience and genetics from the University of Plymouth (UK), Fudan University and Tsinghua University (China).
Writing in the study, the authors say it significantly advances the knowledge available to those working to understand the cause of such inherited conditions.
They are also now planning to conduct further research to fully address the implication of expanded-CAG repeats RNA aggregate toxicity in patients.
The study was co-led by Professor Shouqing Luo, Professor of Neurobiology at the University of Plymouth, and a world-leading expert in HD and other neurodegenerative diseases.
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