Yeast as a Model to Find New Drugs and Drug Targets for -Dependent Neurodegenerative Diseases.

Mutations in human genes result in rare neurological diseases, including chorea-acanthocytosis. The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one gene is present. In this review, we summarize advancements obtained using yeast. In recent studies, Δ and yeast mutants, which are models of chorea-acanthocytosis, were used to screen for multicopy and chemical suppressors. Two of the suppressors, a fragment of the and genes, act by downregulating calcineurin activity. In addition, Δ suppression was achieved by using calcineurin inhibitors. The other group of multicopy suppressors were genes: encoding iron transporter, and , and , encoding copper transporters. Mechanisms of their suppression rely on causing an increase in the intracellular iron content. Moreover, among the identified chemical suppressors were copper ionophores, which require a functional iron uptake system for activity, and flavonoids, which bind iron. These findings point at areas for further investigation in a higher eukaryotic model of -related diseases and to new therapeutic targets: calcium signalling and copper and iron homeostasis. Furthermore, the identified drugs are interesting candidates for drug repurposing for these diseases.