Potential New Source of Genetic Mutations That Cause Neurodegenerative Disease

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 usually 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.

New 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.

Professor Luo said: “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. 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.”

His team has previously shed light on the mechanisms behind autophagy — a process through which cells work to destroy bacteria and viruses after infection — and how it progresses.

He has also established effective ways of facilitating the autophagy process, which results in the mutant huntingtin (HTT) protein in brain cells that causes HD is removed.


Yuyin Pan, Junmei Lu, Xinran Feng, Shengyi Lu, Yi Yang, Guang Yang, Shudan Tan, Liang Wang, Pilong Li, Shouqing Luo, Boxun Lu. Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis. Nature Chemical Biology, 2023; DOI: 10.1038/s41589-023-01384-5

University of Plymouth. “Study uncovers potential new source of genetic mutations that cause neurodegenerative disease.” ScienceDaily. ScienceDaily, 17 August 2023. <www.sciencedaily.com/releases/2023/08/230817163900.htm>.

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Photo by National Cancer Institute