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@ARTICLE{Sahaboglu:145040,
      author       = {Sahaboglu, Ayse and Miranda, Maria and Canjuga, Denis and
                      Avci-Adali, Meltem and Savytska, Natalia and Secer, Enver
                      and Feria-Pliego, Jessica Abigail and Kayık, Gülru and
                      Durdagi, Serdar},
      title        = {{D}rug repurposing studies of {PARP} inhibitors as a new
                      therapy for inherited retinal degeneration.},
      journal      = {Cellular and molecular life sciences},
      volume       = {77},
      number       = {11},
      issn         = {1420-682X},
      address      = {Cham (ZG)},
      publisher    = {Springer International Publishing AG},
      reportid     = {DZNE-2020-00400},
      pages        = {2199-2216},
      year         = {2020},
      abstract     = {The enzyme poly-ADP-ribose-polymerase (PARP) has important
                      roles for many forms of DNA repair and it also participates
                      in transcription, chromatin remodeling and cell death
                      signaling. Currently, some PARP inhibitors are approved for
                      cancer therapy, by means of canceling DNA repair processes
                      and cell division. Drug repurposing is a new and attractive
                      aspect of therapy development that could offer low-cost and
                      accelerated establishment of new treatment options.
                      Excessive PARP activity is also involved in
                      neurodegenerative diseases including the currently
                      untreatable and blinding retinitis pigmentosa group of
                      inherited retinal photoreceptor degenerations. Hence,
                      repurposing of known PARP inhibitors for patients with
                      non-oncological diseases might provide a facilitated route
                      for a novel retinitis pigmentosa therapy. Here, we
                      demonstrate and compare the efficacy of two different PARP
                      inhibitors, BMN-673 and 3-aminobenzamide, by using a
                      well-established retinitis pigmentosa model, the rd1 mouse.
                      Moreover, the mechanistic aspects of the PARP
                      inhibitor-induced protection were also investigated in the
                      present study. Our results showed that rd1 rod photoreceptor
                      cell death was decreased by about $25-40\%$ together with
                      the application of these two PARP inhibitors. The wealth of
                      human clinical data available for BMN-673 highlights a
                      strong potential for a rapid clinical translation into novel
                      retinitis pigmentosa treatments. Remarkably, we have found
                      that the efficacy of 3 aminobenzamide was able to decrease
                      PARylation at the nanomolar level. Our data also provide a
                      link between PARP activity with the Wnt/β-catenin pathway
                      and the major intracellular antioxidant concentrations
                      behind the PARP-dependent retinal degeneration. In addition,
                      molecular modeling studies were integrated with experimental
                      studies for better understanding of the role of PARP1
                      inhibitors in retinal degeneration.},
      keywords     = {Animals / Benzamides: therapeutic use / Drug Repositioning:
                      methods / Humans / Mice / Phthalazines: therapeutic use /
                      Poly(ADP-ribose) Polymerase Inhibitors: therapeutic use /
                      Poly(ADP-ribose) Polymerases: metabolism / Retina: drug
                      effects / Retina: metabolism / Retina: pathology / Retinal
                      Degeneration: drug therapy / Retinal Degeneration:
                      metabolism / Retinal Degeneration: pathology / Retinitis
                      Pigmentosa: drug therapy / Retinitis Pigmentosa: metabolism
                      / Retinitis Pigmentosa: pathology / Benzamides (NLM
                      Chemicals) / Phthalazines (NLM Chemicals) / Poly(ADP-ribose)
                      Polymerase Inhibitors (NLM Chemicals) / 3-aminobenzamide
                      (NLM Chemicals) / talazoparib (NLM Chemicals) /
                      Poly(ADP-ribose) Polymerases (NLM Chemicals)},
      cin          = {AG Heutink},
      ddc          = {610},
      cid          = {I:(DE-2719)1210002},
      pnm          = {345 - Population Studies and Genetics (POF3-345)},
      pid          = {G:(DE-HGF)POF3-345},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31451894},
      doi          = {10.1007/s00018-019-03283-2},
      url          = {https://pub.dzne.de/record/145040},
}