Paramanik V, Thakur M K
Biochemistry and Molecular Biology Laboratory, Centre of Advanced Study, Department of Zoology, Banaras Hindu University, Varanasi, India.
Arch Ital Biol. 2013 Mar;151(1):33-42. doi: 10.4449/aib.v151i1.1461.
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.
在衰老过程中，大脑会发生多种变化，这些变化通过基因表达的改变影响其功能。其中一些基因受雌激素调节，雌激素需要包括CREB在内的许多共调节蛋白。在大脑中，CREB在不同区域表达，并响应包括突触效能和突触可塑性的长期变化在内的各种细胞内信号事件，调节广泛的功能，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诸如cAMP和/或Ca+2等第二信使磷酸化，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信号的改变会导致认知缺陷。在大脑中，CREB的表达随年龄变化，但其随性别变化的情况尚不清楚。因此，在这篇综述论文中，我们总结了最近的研究结果，这些结果表明CREB的表达存在年龄和性别依赖性，以及它与雌激素受体（ER）β的相互作用，以及CREB信号在大脑衰老和疾病中的作用。通过雌激素受体对CREB信号的这种理解可能有助于设计针对与年龄相关的认知缺陷和神经退行性疾病的治疗策略。
