These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS.
Additional homozygous variants were identified, including the risk allele p.Arg261His in NEK1, as well as variants in genes known to be associated with other neurodegenerative diseases, such as HTT (Huntington's disease), ATM (Ataxia-Telangiectasia), and ZFYVE26 (SPG15), and variants in genes previously reported as upregulated (LZTS3) or downregulated (ARMC4, CFAP54, and MTHFSD) in ALS patients.