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Abstract
A range of molecules control nerve-cell survival in the brain. Many of these molecules
might be neuroprotective through activation of the transcription factor cAMP-response-element-binding
protein (CREB). Activation of CREB, by phosphorylation of Ser133, occurs in brain-damage-resistant
hippocampal dentate granule cells and is triggered by neuroprotective environmental
stimulation. In addition, the Akt neuroprotective signaling pathway activates CREB,
and CREB synthesis and phosphorylation promote the survival of many cells, including
neurons, in vitro. Thus, CREB might be responsible for programmed nerve-cell survival.
Studies investigating its role in the brain are now required to confirm these in vitro
results, and the downstream survival genes, whose expression is activated by CREB
in neurons, need to be identified.