MLC-Team

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, genetic brain disease, clinically characterized by early-onset macrocephaly and after a few years slow deterioration of motor functions, epilepsy and mental decline. In MLC, the cerebral myelin is vacuolated, causing white matter swelling. MLC1 is the first gene demonstrated to be involved in this disease. It encodes a transmembrane protein of unknown function. The MLC1 protein is enriched in neurons and in astrocytes. MLC is one of the very few known genetic diseases with astroglial dysfunction. At present, there is no insight into the pathophysiology of MLC; specific therapy is not available. MLC1 mutations are found in 75% of the MLC patients. Genetic linkage studies have demonstrated that there are other, as yet unidentified, disease genes. The planned experiments aim at gaining insight into the disease mechanisms of MLC in order to find openings for treatment. They comprise the characterization of MLC mouse models and the generation and characterization of a zebra fish MLC model. In addition, they include the analysis of cells with decreased MLC1 expression and the characterization of the recently identified MLC1 interactome. Potentially, other MLC disease genes will be found among the related genes. Our multidisciplinary approach will lead to increased insights into the functions of MLC1. We expect that, based on the outcome of the research proposed, we will be able to design screening studies aimed at identifying molecules that could be used for therapy.