All well and good, except that when people looked, the evidence for an actual UPR was, at best, pretty shaky, or not there at all. We still have a lot of questions about the activation of PERK and its close relative, IRE-1, during ischemia, about why the UPR doesn't materialize, and whether the inhibition of protein synthesis during early brain reperfusion is a good thing or not. Clearly, it has to come back eventually if the cell is to live--but when is it too early, if ever? And when is it too late?
Look for answers to these questions and others to emerge from this lab and others over the next few years. In the meantime, it's time to visit with the last remaining Horseman of the Brainocalypse.
The suicidal one. Apoptosis.