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. Author manuscript; available in PMC: 2014 Feb 27.
Published in final edited form as: Neurobiol Dis. 2012 Aug 27;0:13–21. doi: 10.1016/j.nbd.2012.08.016

Figure 7.

Figure 7

Working model of HIF-PHD-mediated neuroprotection and suppression of cancer cell proliferation. HIF-PHD inhibition and the other identified p21 inducers activate the transcription of a broad neuroprotective program that prevents oxidative stress-induced neuronal apoptosis. The breadth of this program precludes the necessity of any single member of the program (i.e. p21 is sufficient to protect, but is unnecessary for the neuroprotective actions of these compounds). Likewise, HIF-PHD inhibitors can induce HIF-dependent cell death, or interfere with PHD-dependent, but HIF-independent survival pathways in cancer cells. It is formally possible that the HIF-PHD targets that mediate neuron death following oxidative stress are the same as those driving tumorigenesis.