Walton M R, Dragunow I
Dept of Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Trends Neurosci. 2000 Feb;23(2):48-53. doi: 10.1016/s0166-2236(99)01500-3.
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.
一系列分子控制着大脑中神经细胞的存活。其中许多分子可能通过激活转录因子环磷酸腺苷反应元件结合蛋白（CREB）发挥神经保护作用。通过Ser133磷酸化激活CREB，发生在抗脑损伤的海马齿状颗粒细胞中，并由神经保护环境刺激触发。此外，Akt神经保护信号通路激活CREB，CREB的合成和磷酸化在体外促进包括神经元在内的许多细胞的存活。因此，CREB可能是程序性神经细胞存活的原因。现在需要开展研究来调查其在大脑中的作用，以证实这些体外实验结果，并且需要鉴定出在神经元中其表达被CREB激活的下游存活基因。
