CREB and cAMP response element-mediated gene expression in the ischemic brain

FEBS J. 2007 Jul;274(13):3210-7. doi: 10.1111/j.1742-4658.2007.05890.x. Epub 2007 Jun 12.


Cerebral ischemia triggers robust phosphorylation of cAMP response element-binding protein (CREB) and CRE-mediated gene expression in neurons. Glutamate receptor activation and subsequent calcium influx may activate CREB shortly after ischemia. CREB activation leads to expression of genes encoding neuroprotective molecules, such as the antiapoptotic protein Bcl-2, and contributes to survival of neurons after ischemic insult. Recent studies have suggested that CREB may be involved in acquisition of ischemic tolerance, a phenomenon that occurs after sublethal ischemic stress. CREB activation is also involved in the survival of newborn neurons in the dentate gyrus of the hippocampus after ischemia. Therefore, CREB-related therapeutics may be promising for brain protection and endogenous neurogenesis and could promote functional recovery in ischemic stroke patients. This minireview summarizes our current understanding for the role of CREB in regulating CRE-mediated gene expression during cerebral ischemia.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Brain Ischemia*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Gene Expression Profiling*
  • Hippocampus / metabolism
  • Humans
  • Hypoxia
  • Mice
  • Models, Biological
  • Neurons / metabolism
  • Oxidative Stress
  • Phosphorylation
  • Signal Transduction


  • Cyclic AMP Response Element-Binding Protein