Role of CREB signaling in aging brain

Abstract

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.