The enzyme poly-ADP-ribose-polymerase (PARP) mediates DNA-repair and rearrangements of the nuclear chromatin. Generally, PARP activity is thought to promote cell survival and in recent years a number of PARP inhibitors have been clinically developed for cancer treatment. Paradoxically, PARP activity is also connected to many diseases including the untreatable blinding disease Retinitis Pigmento...

Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with stroke and neurotrauma. The aim of our study was to evaluate the therapeutic efficacy of in vivo inhibition of PARP in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24g) to the dura vi...

Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhi...

Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive bioma...

Almost all ovarian cancers are comprised of epithelial cancer (EOC). Approximately 80% patients with EOC initially respond to standard cytoreductive therapy and postoperative platinum-based chemotherapy. However, due drug resistance in high-grade serous (HGSOC), recurrence is almost inevitable. Recently, the nuclear enzyme poly (ADP ribose) polymerase (PARP) represents a surprisingly new target...

Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(A...

Ewing sarcoma has recently been reported to be sensitive to poly(ADP)-ribose polymerase (PARP) inhibitors. Searching for synergistic drug combinations, we tested several PARP inhibitors (talazoparib, niraparib, olaparib, veliparib) together with chemotherapeutics. Here, we report that PARP inhibitors synergize with temozolomide (TMZ) or SN-38 to induce apoptosis and also somewhat enhance the cy...

Poly(ADP-ribosyl)ation is a post-translational modification catalyzed by the enzyme family of poly(ADP-ribose) polymerases (PARPs). PARPs exhibit pleiotropic cellular functions ranging from maintenance of genomic stability and chromatin remodeling to regulation of cell death, thereby rendering PARP homologues promising targets in cancer therapy. Depending on the molecular status of a cancer cel...

DNA fragmentation in hepatocytes occurs early after acetaminophen (AAP) overdose in mice. DNA strandbreaks can induce excessive activation of poly(ADP-ribose) polymerases (PARP), which may lead to oncotic necrosis. Based on controversial findings with chemical PARP inhibitors, the role of PARP-1 activation in AAP hepatotoxicity remains unclear. To investigate PARP-1 activation and evaluate a pa...

Poly(ADP-ribose) polymerase-1 (PARP-1) is a NAD-consuming enzyme with an emerging key role in epigenetic regulation of gene transcription. Although PARP-1 expression is characteristically restricted to the nucleus, a few studies report the mitochondrial localization of the enzyme and its ability to regulate organelle functioning. Here, we show that, despite exclusive nuclear localization of PAR...