Although scientists already know that sugar is bad for neurons, a team of Spanish researchers have shown, against the general consensus, that mouse neurons can make long chains of glucose (glycogen), it is just that the machinery to complete this process is kept safety 'locked away' by a complex of two proteins, laforin and malin.
In Lafora disease, this lock appears to be broken through mutations in the genes that produce laofrin and malin.
This rare disease causes irreversible neurodegeneration in adolescents and generally presents as epileptic seizures between 10 to 17 years of age and later on as myoclonus (involuntary twitching of the arms and legs).
Its evolution is marked by progressive degeneration of the nervous system which reduces the patient to a terminal vegetative state ten years after its onset.
No treatment is available.
Joan Guinovart, director of the Institute for Research in Biomedicine (IRB), Barcelona, explained: "We have observed that laforin and malin act jointly as 'guardians' of glycogen levels in neurons and are stimulated by the degradation of the proteins responsible for glucose accumulation."
Specifically they induce the proteasome-dependent degradation of muscle glycogen synthase (MGS) and protein targeting to glycogen (PTG), which helps activate MGS.
"[If] either of the two genes loses its function, these proteins are not degraded, glycogen accumulates and thus neurons deteriorate and cell suicide (apoptosis) ensues."
These findings open up the possibility of finding a drug that could block sugar formation and so treat Lafora disease.
Guinovart collaborated with Santiago Rodríguez de Córdoba, research professor at the Centro Superior de Investigaciones Científicas (CSIC), Spain, and neurobiology expert Eduardo Soriano, who is also a researcher at IRB Barcelona on the research.
Details of the study can be found in the latest issue of Nature Neuroscience.