In 2007, in an article published in Nature Neuroscience, scientists at the Institute for Research in Biomedicine (IRB Barcelona) headed by Joan Guinovart, an authority on glycogen metabolism, reported that in Lafora Disease (LD), a rare and fatal neurodegenerative condition that affects adolescents, neurons die as a result of the accumulation of glycogenchains of glucose. They went on to propose that this accumulation is the root cause of this disease.
The breakthrough of this paper was two-sided: first, the researchers established a possible cause of LD and therefore were able to point to a plausible therapeutic target, and second, they discovered that neurons have the capacity to store glycogenan observation that had never been madeand that this accumulation was toxic.
Some scientists sceptical about the article upheld that the glycogen deposits were not cause by the neurodegeneration but were a consequence of another, more important, cell imbalance, such as a down deregulation of autophagythe cell recycling and cleaning programme. In several articles, Guinovart's "Metabolic engineering and diabetes therapy" group has recently brought to light evidence of the toxicity of glycogen deposits for LD patients, and has now provided irrefutable data.
In an article published at the beginning of February in Human Molecular Genetics, with the associate researcher Jordi Duran as first author, the scientists show that in LD the accumulation of glycogen directly causes neuronal death and triggers cell imbalances such a decrease in autophagy and synaptic failure. All these alterations lead to the symptoms of LD, such as epilepsy.
Glycogen, a Trojan horse for neurons?
There was still a greater mystery to be solved. Was glycogen synthase truly a Trojan horse for neurons, as apparently established in the article in Nature Neuroscience? That is to say, was the accumulation of glycogen alwa
|Contact: Sònia Armengou|
Institute for Research in Biomedicine (IRB Barcelona)