Drosophila melanogaster as a model to study in vivo the functional role of Transposable Elements in Huntington’s Disease pathogenesis

Huntington's disease (HD) is a late-onset disorder characterized by progressive motor dysfunction, cognitive decline and psychiatric disturbances. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a stretch of polyglutamine at the amino terminus of the huntingtin protein. Despite the impressive data that have been accumulated on the molecular basis of neurodegeneration, no cure is still available. It is therefore important to keep investigating potential previously unnoticed pathways that may be altered in HD and target of therapeutic treatments. Transposable elements (TEs) are mobile genetic elements that constitute a large fraction of eukaryotic genomes. Retrotransposons replicate through an RNA intermediate and represent approximately 40% and 30% of the human and Drosophila genomes. Mounting evidences suggest mammalian L1 elements are normally active during neurogenesis. Interestingly, recent reports show that unregulated activation of TEs is associated with neuropathology. Our experimental results obtained in Drosophila HD model, suggest that TE activation may represent an important piece in the complicated puzzle of polyQ-induced neurotoxicity.