摘要：SummaryHuntington's disease (HD) is an autosomal dominant disorder with progressive motor dysfunction and cognitive decline. The disease is caused by a CAG repeat expansion in theIT15gene, which elongates a polyglutamine stretch of the HD protein, Huntingtin. No therapeutic treatments are available, and new pharmacological targets are needed. Retrotransposons are transposable elements (TEs) that represent 40% and 30% of the human andDrosophilagenomes and replicate through an RNA intermediate. Mounting evidence suggests that mammalian TEs are active during neurogenesis and may be involved in diseases of the nervous system. Here we show that TE expression and mobilization are increased in aDrosophila melanogasterHD model. By inhibiting TE mobilization with Reverse Transcriptase inhibitors, polyQ-dependent eye neurodegeneration and genome instability in larval brains are rescued and fly lifespan is increased. These results suggest that TE activation may be involved in polyQ-induced neurotoxicity and a potential pharmacological target.Graphical abstractDisplay OmittedHighlights•Transposable elements: new pathogenic players in Huntington's disease•polyQ-Htt expression leads to widespread heterochromatin relaxation•Reverse transcriptase inhibitors rescue HD-induced neurodegenerationBiological sciences; Molecular biology; Neuroscience
