Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow (India).
Drug Res (Stuttg). 2022 Feb;72(2):65-71. doi: 10.1055/a-1657-2464. Epub 2022 Jan 3.
It is well recognized that cyclic adenosine monophosphate (cAMP) signaling within neurons plays a key role in the foundation of long-term memories. Memory storage is the process that demands the movement of signals, neural plasticity, and the molecules which can transfer the signals from the sensory neuron to the dorsal root ganglion (DRG) neurons and later into the temporal region of the brain. The discovery of cAMP in 1958 as the second messenger also had a role in memory formation and other neural aspects. Further, in 1998 the scientists found that cAMP does not just activate protein kinase A (PKA) but also exchange protein directly activated by cAMP (Epac) which has an active role to play in hyperalgesia, memory, and signaling. The cAMP has three targets, hyperpolarization-activated cyclic nucleotide modulated (HCN) channels, protein kinase A (PKA), and exchange protein activated by cAMP (Epac). Different research has exposed that both PKA and HCN channels are significant for long-term memory creation. Epac is a cAMP-dependent guanine nucleotide exchange factor for the small G proteins including Rap1. However, slight information is there about the role of Epac in this process. The effects of cAMP are predominantly imparted by activating protein kinase A (PKA) and the more newly discovered exchange proteins are directly activated by cAMP 1 and 2 (EPAC1 and EPAC2). This review provides an insight regarding the function and role of both of these secondary messengers in memory and nerve signaling.
人们普遍认为，神经元中的环腺苷酸（cAMP）信号转导在长时记忆的形成中起着关键作用。记忆储存是一个需要信号传递、神经可塑性以及能够将信号从感觉神经元传递到背根神经节（DRG）神经元，然后再传递到大脑颞叶区域的分子的过程。1958 年，cAMP 作为第二信使的发现也与记忆形成和其他神经方面有关。此外，1998 年科学家们发现，cAMP 不仅激活蛋白激酶 A（PKA），还直接激活 cAMP 直接激活的交换蛋白（Epac），它在痛觉过敏、记忆和信号转导中发挥着积极作用。cAMP 有三个靶点，超极化激活环核苷酸调节（HCN）通道、蛋白激酶 A（PKA）和 cAMP 直接激活的交换蛋白（Epac）。不同的研究表明，PKA 和 HCN 通道对于长时记忆的形成都很重要。Epac 是包括 Rap1 在内的小 G 蛋白的 cAMP 依赖性鸟嘌呤核苷酸交换因子。然而，关于 Epac 在这一过程中的作用，人们知之甚少。cAMP 的作用主要是通过激活蛋白激酶 A（PKA）来发挥，而新发现的交换蛋白则直接被 cAMP 1 和 2（EPAC1 和 EPAC2）激活。这篇综述提供了关于这两种第二信使在记忆和神经信号中的功能和作用的深入了解。
