A DROSOPHILA MODEL TO STUDY THE NEURODEGENERATIVE DISEASE DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY

Recently, a group of genetic diseases that causes the degeneration of diverse parts of the nervous system has been shown to have a common mechanism. All the various genes responsible for these diseases are subject to the same mutation that is the cause for the inheritance of the disease and for its stronger and anticipated form in the offspring of patients already affected. Although it is known what genes cause these diseases their function is mostly unclear. Knowledge of their normal roles and of the alterations of their functions in the diseases is a prerequisite for the development of therapeutical approaches. To this aim, it is useful to generate animal models of these pathologies that can help us obtain useful information about the functions of the genes involved. Dentatorubralpallidoluysian atrophy (DRPLA) is one of these syndromes and it is caused by mutations in the atrophin-1 gene. Very recently the equivalent of this gene in the fruit fly, Drosophila melanogaster has been identified and its functions are now being studied. Drosphila is an excellent model organism to understand gene function and interactions among genes since it has been studied for over a century and a great amount of information and useful materials is available. By utilizing the fruit fly and taking advantage of some of the techniques most successfully used in this organism we will try to other genes that interact with atrophin, both in its normal form and in a mutant form similar to that found in DRPLA patients. Beside the understanding of the normal functions of atrophin and of what happens when it is mutated, this approach may lead us to the identification of genes that are able to improve the situation of cells with mutated atrophin. The human equivalent of those genes may then be considered interesting candidates for the cure or amelioration of the disease through gene therapy.