Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of the same coin?

Autophagy. 2008 May;4(4):422-6. doi: 10.4161/auto.5778. Epub 2008 Feb 23.


Autophagy is a homeostatic cellular process required for the recycling of proteins and damaged organelles, and in most scenarios is believed to promote cell survival. However, there is accumulating evidence that under certain pathological situations, autophagy can also trigger and mediate programmed cell death (type II death). Despite the well-established pathophysiological role of apoptosis (type I cell death) in post-ischemic neuron death, there is now increasing interest whether alternative types of programmed cell death might be involved in regulation of neuronal death after both global and focal cerebral ischemia. Initial studies demonstrating the involvement of lysosomal proteases of the cathepsin family in neuron death after global ischemia already had suggested that this type of cell death may occur in an autophagy-dependent manner. Recently it was also shown that focal ischemia is associated with potently enhanced expression of the autophagy regulator Beclin 1 and subcellular redistribution of the autophagic marker LC3 to vacuolic structures in ischemic neurons. Increasing evidence suggests that the effects of autophagy are highly contextual. An insufficient autophagic response might render cells more susceptible to stress conditions whereas on the other hand prolonged overactivation of autophagy can lead to a complete self digestion of the cell. The extent of autophagy may represent a master switch between cell survival and cell death, and it will be of fundamental importance to dissect whether autophagy is primarily a strategy for survival or whether autophagy can also be a part of a cell death program and thus contribute to cell death after cerebral ischemia. A profound understanding of the biological effects and the mechanisms underlying ischemia-induced autophagy in neurons might be helpful in seeking effective new treatments for cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Autophagy / physiology*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Cell Death / physiology*
  • Humans
  • Lysosomes / enzymology
  • Peptide Hydrolases / metabolism


  • Peptide Hydrolases