Neurological Diseases

In a recent work, made in collaboration with K Nowikowsky (Max Perutz, Wien), we analysed the nervous system behavioural and electrophysiological phenotype in Drosophila LETM1 homolog silenced lines. LETM1 is one of the genes linked to the Wolf-Hirschhorn Syndrome, a congenital syndrome characterised by developmental alterations, mental retardation and epilepsy. Another gene which homolog was analysed in collaboration with R.Costa (Dep. of Biology, University of Padova) and M.Zeviani (Istituto Neurologico Besta, Milano) is surf1 which is linked in humans with the Leigh Syndrome, the most commun mitochondrial encephalomiopathy. Using the RNAi technique, D.melanogaster surf1 homolog was silenced by creating transgenic lines bearing the interferring dsRNA against Drosophila surf1 under the control of an UAS promoter. After crossing the transgenic line with a Gal4 line, the Gal4 production in F1 individuals induces the UAS activation in cells expressing Gal4. In this way, using the Gal4/UAS binary system it was possible to silence surf1 ubiquitously or in specific tissues (nervous system or muscle system). On this line are the studies, in collaboration with R.Costa (Dep of Biology, University of Padova) on zasp/cypher, a gene expressing a protein of the Z-line in striated muscle which alteration is responsible of a group of mild dystrophies in humans.Our aim is to specifically disrupt identified homologs in D.melanogaster using the powerful genetics available for this animal model (P-elements or RNAi) and analyse the nervous system phenotype, physiology and morphology in mutant lines.Between 60 to 70 % homologs of genes associated to inherited human genetic diseases are present in Drosophila melanogaster genome. Among these are genes linked to inherited nervous system diseases and also to other neurologic disturbances of uncertain origin like Alzheimer disease, Parkinsons disease, Schizophrenia or epilepsy.