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Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult and aged rat hippocampus.

100%

Strosznajder J. B., Jęśko H., Strosznajder R. P.

Acta Biochimica Polonica

2000

vol. 47

issue 3

847-854

It is suggested that the fibrillar amyloid beta peptide (Aβ) in brain plays a direct role in neurodegeneration in Alzheimer's disease, probably through activation of reactive oxygen species formation. Free radicals and numerous neurotoxins elicit DNA damage that subsequently activates poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30). In this study the effect of neurotoxic fragment (25-35) of full length Aβ peptide on PARP activity in adult and aged rat hippocampus was investigated. In adult (4 month old) rat hippocampus the Aβ 25-35 peptide significantly enhanced PARP activity by about 80% but had no effect on PARP activity in cerebral cortex and in hippocampus from aged (24-27 month old) rats. The effect of Aβ peptide was reduced by half by the nitric oxide synthase inhibitor N-nitro-L-arginine. Stimulation of glutamate receptor(s) itself enhanced PARP activity by about 80% in adult hippocampus. However, Aβ 25-35 did not exert any additional stimulatory effect. These results indicate that Aβ, through NO and probably other free radicals, induces activation of DNA bound PARP activity exclusively in adult but not in aged hippocampus.

Poly(adP-ribose) polymerase inhibitor olaparib in the treatment of ovarian cancer: a comprehensive review of current literature

86%

Poboży K., Domańska J., Domański P.

OncoReview

2023

vol. 13

issue 2

39-47

Purpose of the review: This comprehensive review aims to provide a summary of current research on the utilization of olaparib, a poly(ADP-ribose) polymerase (PArP) inhibitor, in the treatment of ovarian cancer. The review aims to highlight the key findings from recent clinical trials and assess the potential of olaparib as a targeted therapy for improving the prognosis of ovarian cancer patients. recent findings: Ovarian cancer remains a significant global health concern with high mortality rates. While optimal debulking surgery and platinum-based chemotherapy are the standard treatments, the recurrence rates remain substantial. The emergence of PArP inhibitors, particularly olaparib, has intro duced a novel therapeutic approach that targets the genomic instability and DnA repair mechanisms in cancer cells. notable clinical trials, such as SOl O1, SOl O2, and PAOlA-1, have demonstrated the effectiveness of olaparib in significantly improving progression-free survival, particularly in patients with Br CA mutations or homologous recombination deficiency. Additionally, combination therapies involving olaparib, such as those with bevacizumab or entinostat, have shown promising results. Summary: The utilization of olaparib has brought about a paradigm shift in the treatment of ovarian cancer. notably, it has shown significant improvements in progression-free survival and overall survival, particularly in patients with Br CA mutations or homologous recombination deficiency. The exploration of olaparib through various clinical trials and combination therapies continues to provide valuable insights and offer new prospects for ovarian cancer patients. Moreover, the growing understanding of PArP inhibitors holds the potential for further advancements in the prognosis of patients with this formidable condition.

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1 Strosznajder J. B.

1 Strosznajder R. P.

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Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult and aged rat hippocampus.

Poly(adP-ribose) polymerase inhibitor olaparib in the treatment of ovarian cancer: a comprehensive review of current literature