Huntington's disease (HD) is a late-onset, autosomal dominant disorder characterized by progressive motor dysfunction, cognitive decline and psychiatric disturbances. The most prominent pathological manifestation is a selective loss of medium sized spiny neurons of the striatum. 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 HD protein, Huntingtin (Htt). Despite the accumulation of an impressive amount of data 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 evidence suggests mammalian L1 elements are normally active during neurogenesis. Interestingly, recent reports show that unregulated activation of TE is associated with neuropathology.
Our experimental preliminary results obtained in Drosophila melanogaster HD model, suggest that TEs activation may represent an important piece in the complicated puzzle of polyQ-induced neurotoxicity.
