For example, in ataxia telangiectasia (A-T), spinocerebellar ataxia with axonal neuropathy (SCAN1) and amyotrophic lateral sclerosis/ frontotemporal dementia (ALS/FTD) models, the defects in TOP1cc repair and consequent accumulation of DSBs over time were shown to trigger neuronal death [20–23]. This evidence concerns the gene TDP1 and amyotrophic lateral sclerosis.