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Docosahexaenoic acid and tetracyclines as promising neuroprotective compounds with poly(ADP-ribose) polymerase inhibitory activities for oxidative/genotoxic stress treatment
Authors:Magdalena Cieslik  Joanna PyszkoJoanna B. Strosznajder
Affiliation:Medical Research Center, Polish Academy of Sciences, Department of Cellular Signaling, Pawinskiego 5 Str., 02-106 Warsaw, Poland
Abstract:The human genome is exposed to oxidative/genotoxic stress by several endogenous and exogenous compounds. These events evoke DNA damage and activate poly(ADP-ribose) polymerase-1 (PARP-1), the key enzyme involved in DNA repair. The massive stress and over-activation of this DNA-bound enzyme can be responsible for an energy crisis and neuronal death. The last data indicated that product of PARP-1, i.e. poly(ADP-ribose) (PAR), acts as a signalling molecule and plays a significant role in nucleus-mitochondria cross-talk. PAR translocated to the mitochondria can be involved in mitochondrial permeability, the release of an apoptosis-inducing factor (AIF). Its translocation into the nucleus leads to chromatin condensation, fragmentation and cell death. The exact mechanism of this novel death pathway has not yet fully been understood.
Keywords:Oxidative stress   Genotoxic stress   DHA   Tetracyclines   MNNG   Neuronal cell death
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