During aging, brain undergoes several changes which influence its function through alteration in the expression of genes. Some of these genes are regulated by estrogen which requires a host of coregulator proteins including CREB. In brain, CREB is expressed in different regions and regulates a wide range of functions such as cellular growth, proliferation and memory in response to a variety of intracellular signaling events including synaptic efficacy and long-lasting changes in synaptic plasticity. In response to signals at the cell surface, CREB is phosphorylated in the nucleus by various protein kinases via secondary messengers such as cAMP and/or Ca+2 for regulating specific genes. Alterations in CREB signaling lead to cognitive deficits as observed in normal aging and neurodegenerative diseases. In brain, the expression of CREB changes with age, but its variation with sex is not known. So, in this review paper, we summarize recent findings indicating age and sex dependent expression of CREB and its interaction with estrogen receptor (ER)β, and the role of CREB signaling in brain aging and diseases. Such understanding of CREB signaling through ER may help to design therapeutic strategies for age related cognitive deficits and neurodegenerative disorders.

中文翻译：

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CREB信号在大脑衰老中的作用。

在衰老过程中，大脑会经历多种变化，这些变化会通过基因表达的改变影响其功能。这些基因中的一些受雌激素调节，雌激素需要包括CREB在内的多种调节核心蛋白。在大脑中，CREB在不同区域表达，并响应各种细胞内信号传导事件（包括突触效力和突触可塑性的长期变化）来调节多种功能，例如细胞生长，增殖和记忆。响应细胞表面的信号，CREB在细胞核中被各种蛋白激酶通过辅助信使（例如cAMP和/或Ca + 2）磷酸化，以调节特定基因。如在正常衰老和神经退行性疾病中所观察到的，CREB信号传导的改变导致认知缺陷。在大脑中 CREB的表达随年龄而变化，但其随性别的变化尚不清楚。因此，在这篇综述文章中，我们总结了最近的发现，这些发现表明了CREB的年龄和性别依赖性表达及其与雌激素受体（ER）β的相互作用，以及CREB信号在脑衰老和疾病中的作用。通过ER对CREB信号的这种理解可能有助于设计针对年龄相关的认知缺陷和神经退行性疾病的治疗策略。