Streptozotocin (STZ) selectively destroys insulin-producing beta islet cells of the pancreas providing a model of type I diabetes. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme whose overactivation by DNA strand breaks depletes its substrate NAD+ and then ATP, leading to cellular death from energy depletion. We demonstrate DNA damage and a major activation of PARP in pancreatic islets ...

Inhibitors of poly(ADP-ribose) polymerase (PARP) are promising anticancer drugs, particularly for the treatment of tumors deficient in the DNA damage response (DDR). However, it is challenging to design effective therapeutic strategies for use of these compounds against cancers without DDR deficiencies. In this context, combination therapies in which PARP inhibitors are used alongside DDR inhib...

CHK2 is a checkpoint kinase involved in the ATM-mediated response to double-strand DNA breaks. Its potential as a drug target is still unclear, but inhibitors of CHK2 may increase the efficacy of genotoxic cancer therapies in a p53 mutant background by eliminating one of the checkpoints or DNA repair pathways contributing to cellular resistance. We report here the identification and characteriz...

Poly (ADP-ribose) polymerases (PARP) are a family of nuclear protein enzymes involved in the DNA damage response. The role of PARP-1 in base excisional repair has been extensively characterized. More recent in vitro studies additionally implicate a role for PARP-1 in facilitating homologous recombination and nonhomologous end-joining. The more faithful process of homologous recombination repair...

Vitamin D is well characterized for its role in mineral homeostasis and maintenance of normal skeletal architecture. Vitamin D has been demonstrated to exert anti-inflammatory effects in a variety of disease states including diabetes, arthritis and inflammatory bowel disease. In these diseases poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP) inhibitors have also proved effective as an...

Poly (ADP-ribose) polymerases (PARP) are a family of nuclear protein enzymes involved in the DNA damage response. The role of PARP-1 in base excisional repair has been extensively characterized. More recent in vitro studies additionally implicate a role for PARP-1 in facilitating homologous recombination and nonhomologous end-joining. The more faithful process of homologous recombination repair...

Oxidative stress can cause DNA breaks which induce activation of the DNA nick sensor enzyme poly(ADP-ribose) polymerase-1 (PARP-1), part of the 17 member PARP enzyme family. PARP-1 modifies target proteins by attaching to them several NAD-derived ADP-ribose units forming poly(ADP-ribose) (PAR) polymers. PARylation controls many cellular processes while intense PARylation may also lead to cell d...

Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options. We previously found that PARP is overexpressed in SCLC and that targeting PARP reduces cell line and tumor growth in preclinical models. However, SCLC cell lines with PI3K/mTOR pathway activation were relatively less sensitive to PARP inhibition. In this study, we investigated the proteomic changes in PI3K...

Purpose of the review: This comprehensive review aims to provide a summary current research on utilization olaparib, poly(ADP-ribose) polymerase (PARP) inhibitor, in treatment ovarian cancer. The highlight key findings from recent clinical trials and assess potential olaparib as targeted therapy for improving prognosis cancer patients.
 Recent findings: Ovarian remains significant global h...