“…In addition, recent studies using DNA damaging agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), hydrogen peroxide (H 2 O 2 ) or peroxynitrite, which are well known to induce necrosis at high concentrations, showed that pharmacological inhibition of PARP-1 activity or knockout of the PARP-1 gene blocks programmed-necrotic cell death induced by these agents [14,17,18]. All together these evidences lead to the hypothesis of using inhibitors of PARP-1 gene as a protective therapy also to prevent neurodegeneration and premature aging in individuals with DS.…”