Recent findings in basic biomedical research might pave the way towards novel therapies
Scientists at the Max Planck Institute for Biology of Ageing in Cologne and University College London have now unearthed the way in which a specific genetic mutation leads to neuronal damage in two serious afflictions, that might even occur at once in a single person: Until now, it has been unknown what causes amyotrophic lateral sclerosis and frontotemporal dementia.
Amyotrophic lateral sclerosis is a devastating type of motor neuron disease that causes rapid weakening of muscles and death. Frontotemporal dementia is the second most common cause of dementia in people under 65. It causes distressing symptoms, including changes in personality and behaviour and problems with language and thinking.
The DNA of affected patients contains a mutation: There are thousands of repeats of a specific short segment of genetic material, whereas in unaffected persons, there are only up to thirty copies of this segment. This specific genetic alteration is the cause of illness in around eight percent of patients with this type of motor neuron disease or dementia. Eight percent is a relatively high proportion. For instance, less than one percent of the causes in Alzheimer’s disease are genetic.
Researchers at the Max Planck Institute for Biology of Ageing, the Institute of Neurology and Institute for Healthy Ageing at University College London have now discovered that the repeats in the mutant gene cause neurodegeneration by making toxic proteins.
Fruitflies can undergo neurodegeneration in a similar way to humans
Previously it was thought that the problem could be a consequence of disruption of the gene by the inserted repeats. Another theory was that the repeats produce a different type of toxic RNA molecule. It now turns out that the repeats in the mutant gene can produce a variety of proteins and that two of these are extremely toxic to nerve cells. Both are highly enriched in arginine, an amino acid.
To pinpoint the role of the toxic proteins, the researchers produced artificial repeat segments that could produce potentially toxic RNA and protein or only toxic RNA or only protein. They then introduced them into the nerve cells of fruit flies, which can undergo neurodegeneration in a similar way to humans. Repeat segments that made both RNA and protein caused striking neurodegeneration and reduced the lifespan of the flies, showing that they are a good organism in which to study these diseases. Interestingly, the protein-only repeat segments caused just as bad a neurodegeneration. In contrast, the RNA-only segments were harmless, pinpointing the role of toxic proteins in these diseases. The proteins that contained arginine were the most toxic.
These findings have uncovered a new toxic role for arginine-containing proteins in motor neuron disease and dementia, which helps in the development of drugs to fight these serious afflictions.
C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins.
Sarah Mizielinska, Sebastian Grönke, Teresa Niccoli, Charlotte E. Ridler, Emma L. Clayton, Anny Devoy, Thomas Moens, Frances E. Norona, Ione O.C. Woollacott, Julian Pietrzyk, Karen Cleverley, Andrew J. Nicoll, Stuart Pickering-Brown, Jacqueline Dols, Melissa Cabecinha, Oliver Hendrich, Pietro Fratta, Elizabeth M.C. Fisher, Linda Partridge, and Adrian M. Isaacs.
Science Express, August 7, 2014.
Sabine Dzuck | Max-Planck-Institut
Biology in a twist -- deciphering the origins of cell behavior
31.03.2015 | National University of Singapore
Speech dynamics are coded in the left motor cortex
31.03.2015 | Universitätsmedizin Göttingen - Georg-August-Universität
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
31.03.2015 | Life Sciences
31.03.2015 | Materials Sciences
31.03.2015 | Earth Sciences