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

Huntington's disease (HD) is a late-onset, autosomal dominant disorder characterized by progressive motor dysfunction, early death, cognitive decline and psychiatric disturbances. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a stretch of polyglutamine (polyQ) at the amino-terminus of the HD protein, huntingtin (Htt). Despite the impressive data that have been accumulated on the molecular basis of neurodegeneration, no cure is still available. 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 evidence suggests mammalian L1 elements are normally active during neurogenesis. Interestingly, recent reports show that a deregulated TE activation is associated with neurodegenerative diseases. Drosophila melanogaster is an excellent model for studying HD pathology and disease mechanisms, because the majority of pathological features can be recapitulated in transgenic fly models. Our experimental results suggest that TEs represent an important piece in the complicated puzzle of polyQ-induced neurotoxicity.