Differential gene expression analysis in S-phase neurons derived from L1-GFP/5xFAD and L1-GFP mice

Here, we demonstrate that aberrant cell cycle reentry (CCR) is prominent in mature neurons and the replication fork in S-phase neurons acts as a target site for retrotransposition by long interspersed nuclear element-1 (L1) in neurodegeneration-prone 5xFAD mice.

Interestingly, the morbid susceptibility of S-phase neurons to cell death has been attributed to enhanced L1 retrotransposition and DNA repair deficiency. Furthermore, deficit in sirtuin 6 expression and estrogen/prolactin signaling promote stochastic L1 retrotransposition and impair Brca1 expression in S-phase neurons, respectively. Importantly, L1 retrotransposition-related neuronal malfunction is correlated with conventional AD pathology.