NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death.

@article{Alano2010NADDI,
  title={NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death.},
  author={Conrad C. Alano and Philippe Garnier and Weihai Ying and Youichirou Higashi and Tiina M. Kauppinen and Raymond A Swanson},
  journal={The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year={2010},
  volume={30 8},
  pages={2967-78}
}
Poly(ADP-ribose)-1 (PARP-1) is a key mediator of cell death in excitotoxicity, ischemia, and oxidative stress. PARP-1 activation leads to cytosolic NAD(+) depletion and mitochondrial release of apoptosis-inducing factor (AIF), but the causal relationships between these two events have been difficult to resolve. Here, we examined this issue by using extracellular NAD(+) to restore neuronal NAD(+) levels after PARP-1 activation. Exogenous NAD(+) was found to enter neurons through P2X(7)-gated… CONTINUE READING
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