Lafora Progressive Myoclonus Epilepsy
Lafora progressive myoclonus epilepsy is a fatal form of autosomal recessive neurodegenerative disorder that is characterized by the presence of insoluble polyglucosan inclusion bodies, known as Lafora bodies. They are generally found in many of the body’s tissues such as within the cytoplasm of the cells of the heart, liver, muscle, and skin but the signs and symptoms of the disease are limited to the nervous system.
The disease presents with epileptic seizures followed by progressive central nervous system degeneration beginning with myoclonic seizures, tonic-clonic seizures, focal occipital seizures, intellectual decline, severe motor and coordination deterioration, and constant myoclonus (Gentry, Worby, and Dixon, 2005). The onset of clinical …show more content…
proposed two scenarios that explain the mechanism of the two proteins behind the disease (2005). In the first scenario, laforin and malin work on the same substrate (protein X) and promote its degradation. Protein X would be dephosphorylated by laforin, which can be subsequently ubiquitinated by malin for its degradation. In this case, degradation of protein X allows for proper glycogen metabolism and it is the accumulation of protein X in the absence of functional malin that results in Lafora disease. In the second scenario, laforin acts both as an activator and repressor of proper glycogen metabolism. Laforin dephosphorylates protein X and laforin is polyubiquitinated and degraded subsequently by malin, and this event allows for the proper glycogen construction or inhibition of abnormal glycogen accumulation. In this case, mutation in malin that results in the failure of polyubiquitination of laforin or mutation in laforin that results in the failure of dephosphorylation of protein X would result in aberrant glycogen metabolism and consequently lead to Lafora disease. A more recent study done by Roma-Mateo et al. shows that laforin interacts physically with malin and the laforin-malin complex controls glycogen synthesis by specific ubiquitinating and promoting the proteasome-degradation of neuronatin, an 81 amino acid protein that stimulates glycogenesis
The disease presents with epileptic seizures followed by progressive central nervous system degeneration beginning with myoclonic seizures, tonic-clonic seizures, focal occipital seizures, intellectual decline, severe motor and coordination deterioration, and constant myoclonus (Gentry, Worby, and Dixon, 2005). The onset of clinical …show more content…
proposed two scenarios that explain the mechanism of the two proteins behind the disease (2005). In the first scenario, laforin and malin work on the same substrate (protein X) and promote its degradation. Protein X would be dephosphorylated by laforin, which can be subsequently ubiquitinated by malin for its degradation. In this case, degradation of protein X allows for proper glycogen metabolism and it is the accumulation of protein X in the absence of functional malin that results in Lafora disease. In the second scenario, laforin acts both as an activator and repressor of proper glycogen metabolism. Laforin dephosphorylates protein X and laforin is polyubiquitinated and degraded subsequently by malin, and this event allows for the proper glycogen construction or inhibition of abnormal glycogen accumulation. In this case, mutation in malin that results in the failure of polyubiquitination of laforin or mutation in laforin that results in the failure of dephosphorylation of protein X would result in aberrant glycogen metabolism and consequently lead to Lafora disease. A more recent study done by Roma-Mateo et al. shows that laforin interacts physically with malin and the laforin-malin complex controls glycogen synthesis by specific ubiquitinating and promoting the proteasome-degradation of neuronatin, an 81 amino acid protein that stimulates glycogenesis