TY  - JOUR
AU  - Sahaboglu, Ayse
AU  - Miranda, Maria
AU  - Canjuga, Denis
AU  - Avci-Adali, Meltem
AU  - Savytska, Natalia
AU  - Secer, Enver
AU  - Feria-Pliego, Jessica Abigail
AU  - Kayık, Gülru
AU  - Durdagi, Serdar
TI  - Drug repurposing studies of PARP inhibitors as a new therapy for inherited retinal degeneration.
JO  - Cellular and molecular life sciences
VL  - 77
IS  - 11
SN  - 1420-682X
CY  - Cham (ZG)
PB  - Springer International Publishing AG
M1  - DZNE-2020-00400
SP  - 2199-2216
PY  - 2020
AB  - 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
KW  - Animals
KW  - Benzamides: therapeutic use
KW  - Drug Repositioning: methods
KW  - Humans
KW  - Mice
KW  - Phthalazines: therapeutic use
KW  - Poly(ADP-ribose) Polymerase Inhibitors: therapeutic use
KW  - Poly(ADP-ribose) Polymerases: metabolism
KW  - Retina: drug effects
KW  - Retina: metabolism
KW  - Retina: pathology
KW  - Retinal Degeneration: drug therapy
KW  - Retinal Degeneration: metabolism
KW  - Retinal Degeneration: pathology
KW  - Retinitis Pigmentosa: drug therapy
KW  - Retinitis Pigmentosa: metabolism
KW  - Retinitis Pigmentosa: pathology
KW  - Benzamides (NLM Chemicals)
KW  - Phthalazines (NLM Chemicals)
KW  - Poly(ADP-ribose) Polymerase Inhibitors (NLM Chemicals)
KW  - 3-aminobenzamide (NLM Chemicals)
KW  - talazoparib (NLM Chemicals)
KW  - Poly(ADP-ribose) Polymerases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31451894
DO  - DOI:10.1007/s00018-019-03283-2
UR  - https://pub.dzne.de/record/145040
ER  -