| First Author | Martire S | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 9 | Pages | e72169 |
| PubMed ID | 24086258 | Mgi Jnum | J:206023 |
| Mgi Id | MGI:5547667 | Doi | 10.1371/journal.pone.0072169 |
| Citation | Martire S, et al. (2013) PARP-1 modulates amyloid beta peptide-induced neuronal damage. PLoS One 8(9):e72169 |
| abstractText | Amyloid beta peptide (Abeta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Abeta25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Abeta25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Abeta25-35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Abeta25-35 induces DNA damage which in turn activates PARP-1. Challenge with Abeta25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Abeta25-35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Abeta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed. |
