Figure 3 summarises our current understanding of how DNA damage induces neurodegeneration in ALS. Given the link between TDP-43 pathology and DNA damage, it is possible that therapies that target the DDR may be widely applicable in ALS, such as PARP-1 inhibitors, which are known to inhibit neuronal death. However these approaches have not been evaluated clinically (Thapa et al., 2021). Here, PARP1 is linked to amyotrophic lateral sclerosis.