https://www.researchgate.net/figure/49622906_fig3_Figure-1-Caspase-independent-cell-death-cascade-Ischaemia-causes-calcium-influx-through
Figure
1: Caspase-independent cell death cascade. Ischaemia causes calcium
influx through multiple channels including, N-methyl-D-aspartate (NMDA)
receptor, acid sensing ion channel (ASIC), and TRPM7, which leads to
increased neuronal nitric oxide synthase (nNOS), and generation of
peroxynitrite (ONOO−) from nitric oxide (NO) and superoxide (O2−),
damaging DNA. O2− is generated from NMDA receptor activation of
nicotinamide adenine dinucleotide phosphate oxidase. The DNA repair
enzyme poly-ADP-ribose polymerase-1 (PARP-1) is activated utilizing
cellular nicotinamide adenine dinucleotide (NAD+) forming
poly-ADP-ribose (PAR) polymers, which cause nuclear translocation of
apoptosis inducing factor (AIF) further damaging DNA. Cell death occurs
from AIF-mediated DNA degradation and NAD+ depletion causing energy
failure. What plays the role of executioner?
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