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. Author manuscript; available in PMC: 2012 Sep 1.
Published in final edited form as: Acta Physiol (Oxf). 2011 Jan 19;203(1):225–234. doi: 10.1111/j.1748-1716.2010.02229.x

Figure 1.

Figure 1

Caspase-Independent Cell Death Cascade. Ischemia causes calcium influx through multiple channels including, NMDA, ASIC, and TRPM7, which leads to increased neuronal nitric oxide synthase (nNOS), and generation of peroxynitrite (ONOO) from nitric oxide (NO) and superoxide (O2), damagings DNA. O2 is generated from NMDA receptor activation of NADPH oxidase. The DNA repair enzyme PARP-1 is activated utilizing cellular NAD+ forming PAR polymers, which cause nuclear translocation of AIF further damaging DNA. Cell death occurs from AIF-mediated DNA degradation and NAD+ depletion causing energy failure. What plays the role of executioner?