Glycogen accumulation in neurons causes brain damage and shortens the lives of flies and mice

This image shows a cerebellum sample from a healthy mouse. Credit: Jordi Duran (IRB Barcelona)

Collaborative research by groups headed by scientists Joan J. Guinovart and Marco Milán at the Institute for Research in Biomedicine (IRB Barcelona) has revealed conclusive evidence about the harmful effects of the accumulation of glucose chains (glycogen) in fly and mouse neurons.

These two animal models will allow scientists to address the genes involved in this harmful process and to find pharmacological solutions that allow disintegration of the accumulations or limitation of production. Advances in this direction would make a significant contribution to investigation into Lafora progressive myoclonic epilepsy and other neurodegenerative diseases characterized by glycogen accumulation in . The journal EMBO Molecular Medicine publishes the results of the study this week.

This image shows the same tissue (mouse cerebellum) after glycogen accumulation. Credit: Jordi Duran (IRB Barcelona)

"Our data clearly indicate that glycogen accumulation alone kills neurons and thus dramatically reduces lifespan", explains Guinovart, an expert in glycogen metabolism, group leader at IRB Barcelona, and senior professor at the University of Barcelona, "because the only thing we have manipulated in the neurons is their capacity to produce glycogen".

The inclusion of the Drosophila fly in the study provides in vivo confirmation of the theory in another animal model as these flies also show the same symptoms of degeneration as mice when glycogen accumulates in neurons. However, in addition the use of Drosophila will speed up obtaining genetic data and the screening of therapeutic molecules. "In a short time we will be able to perform a massive search for genes involved in the pathological process and to understand it better at the molecular level", emphasizes Marco Milán, ICREA researcher at IRB Barcelona and a specialist in Drosophila. "But the flies will also be useful to identify pharmacological molecules that can cure", he explains.

The IRB Barcelona teams are designing several experiments to identify the possible therapeutic targets that may be useful to prevent glycogen accumulation in neurons. In addition to the direct relation to Lafora epilepsy, a progressive degenerative disease that affects adolescents and has no cure, glycogen accumulation could be the main cause of other neurodegenerative illnesses such as Adult polyglucosan body disease and Andersen's disease.

Related Stories

Mouse model brings new perspectives on Lafora disease

date Aug 29, 2011

Short-term energy storage in animal cells is usually achieved through the accumulation of glucose, in the form of long and branched chains, known as glycogen. But when this accumulation happens in neurons it is fatal, causing ...

Answers to a rare and tragic form of epilepsy

date Mar 01, 2011

A new study offers critical insight into the biochemistry of a rare and fatal form of epilepsy known as Lafora disease, a genetic condition that typically strikes children in their teens. The disease is characterized ...

Genetic variant impairs glycogen synthesis

date Jan 29, 2008

Glycogen is stored in skeletal muscles and liver and is of central importance as a first source of energy for muscle contractions, especially during high intensity exercise. Human genetic disorders primarily affecting skeletal ...

Recommended for you

Diet rich in methionine may promote memory loss

date 20 hours ago

Memory loss has recently been associated with excessive silencing of genes through a process called methylation. Researchers at the University of Louisville investigated the effects of a diet rich in methionine—an amino ...

Intelligent neuroprostheses mimic natural motor control

date Mar 30, 2015

Neuroscientists are taking inspiration from natural motor control to design new prosthetic devices that can better replace limb function. In new work, researchers have tested a range of brain-controlled devices ...

Researchers create 'Wikipedia' for neurons

date Mar 30, 2015

The decades worth of data that has been collected about the billions of neurons in the brain is astounding. To help scientists make sense of this "brain big data," researchers at Carnegie Mellon University ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.