TY - JOUR T1 - LINE-1 repression attenuates degeneration in adult dopaminergic neurons JF - bioRxiv DO - 10.1101/164608 SP - 164608 AU - François-Xavier Blaudin de Thé AU - Hocine Rekaik AU - Eugenie Peze-Heidsieck AU - Olivia Massiani-Beaudoin AU - Rajiv L. Joshi AU - Julia Fuchs AU - Alain Prochiantz Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/19/164608.abstract N2 - Long Interspersed Nuclear Elements (LINEs) retrotransposons are emerging as possible players in development and disease. We report here that the three main active LINE-1 families are expressed in post-mitotic dopaminergic neurons of the substantia nigra pars compacta, a class of ventral midbrain neurons that degenerate in Parkinson disease. The progressive degeneration of dopaminergic neurons in mice heterozygote for Engrailed-1 that starts at 6 weeks of age is paralleled by an increase in LINE-1 expression. Similarly, DNA damage and cell death induced by an acute oxidative stress specifically applied to these neurons is accompanied by enhanced LINE-1 expression. Following these observations, we demonstrate that LINE-1 overexpression is key to oxidative stress-induced neuronal death. Reduction of LINE-1 activity through direct transcriptional repression by Engrailed, a siRNA directed against LINE-1, the nucleoside-analogue reverse transcriptase inhibitor stavudine or viral Piwil1 expression, protects dopaminergic neurons against degeneration. ER -