A gene mutation causing Purkinje cell degeneration and ataxia-like symptoms in a mouse model has been identified by a team of scientists. The team, led by Dr Marija Kojic and Professor Brandon Wainwright from The University of Queensland’s Institute for Molecular Bioscience (IMB) and Dr Sebastian Glatt from Jagiellonian University in Krakow, made the findings in a study of cerebellar ataxias.
Cerebellar ataxias are caused by damage to the cerebellum, the part of the brain that controls motor function.
“These rare but devastating conditions get worse over time, causing poor coordination, unsteady walking, difficulty speaking and swallowing, and difficulty performing fine motor skills such as buttoning a shirt. While they are often caused by environmental factors such as alcohol, these conditions also have genetic causes, which have so far been largely unexplored. For the first time, we have found a link between ataxias and a mutation of the Elongator gene, which regulates how our brain cells produce proteins,”
Dr Kojic explained.
The researchers discovered this mutation slows production of the proteins that neurons need to function, causing them to gradually degenerate.
Professor Wainwright said the team also uncovered a link between inflammation of brain cells and brain degeneration, including ataxias.
“Our study revealed inflammation in the cells surrounding the degenerated cells. While this is not unusual, we found that blocking this inflammation slowed the rate at which the cells were dying. This effect occurs across a broad range of neuro-degenerative conditions, such as Alzheimer’s disease, Parkinson’s disease and motor neurone disease, which has profound implications for the treatment of these diseases.
We may not be able to stop this neurological degeneration but if we can slow it down – for example, so a disease takes 20 years to progress, rather than 10 – this could have a huge impact on the health and quality of life of people living with these conditions,”
Wainwright said. Ataxias are progressive and currently incurable disorders, but this research offers hope for the future.
The work was supported by a grant from the National Science Centre, Poland, funding from the European Union’s Horizon 2020 research and innovation program, and from the Foundation for Polish Science.
Marija Kojic, Monika Gaik, Bence Kiska, Anna Salerno-Kochan, Sarah Hunt, Angelo Tedoldi, Sergey Mureev, Alun Jones, Belinda Whittle, Laura A. Genovesi, Christelle Adolphe, Darren L. Brown, Jennifer L. Stow, Kirill Alexandrov, Pankaj Sah, Sebastian Glatt & Brandon J. Wainwright
Elongator mutation in mice induces neurodegeneration and ataxia-like behavior
Nature Communications volume 9, Article number: 3195 (2018)
Last Updated on November 9, 2022