Drosophila model of Spinocerebellar Ataxia type 3 used as part of an effort to identify drug targets for treatment of this ataxia

Ashraf NS, Sutton JR, Yang Y, Ranxhi B, Libohova K, Shaw ED, Barget AJ, Todi SV, Paulson HL, do Carmo Costa M. Druggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia type 3 disease protein. Neurobiol Dis. 2019 Nov 26:104697. PMID: 31783119.

From the abstract: "Spinocerebellar Ataxia type 3 (SCA3, also known as Machado-Joseph disease) is a neurodegenerative disorder ... No preventive treatment is yet available for SCA3. ... Here, we sought to identify genes that modulate ATXN3 levels as potential therapeutic targets in this fatal disorder. We screened a collection of siRNAs targeting 2742 druggable human genes using a cell-based assay ... Among the 33 genes confirmed in secondary assays, 15 were validated in an independent cell model as modulators of pathogenic ATXN3 protein levels. Ten of these genes were then assessed in a Drosophila model of SCA3, and one was confirmed as a key modulator of physiological ATXN3 abundance in SCA3 neuronal progenitor cells. ... Among identified pathways highlighted by this screen, the FBXL3/SCF axis represents a novel molecular pathway that regulates physiological levels of ATXN3 protein."