Key Laboratory of Xin'an Medicine, The Ministry of Education and Key Laboratory of Molecular Biology (Brain diseases), Anhui University of Chinese Medicine, Hefei 230012, China.
Acupuncture and Moxibustion Clinical Medical Research Center of Anhui Province, The Second Affiliation Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.
Cell Signal. 2024 Oct;122:111311. doi: 10.1016/j.cellsig.2024.111311. Epub 2024 Jul 24.
Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is derived from the conversion of adenosine triphosphate catalysed by adenylyl cyclase (AC). Protein kinase A (PKA), the main effector of cAMP, is a dimeric protein kinase consisting of two catalytic subunits and two regulatory subunits. When cAMP binds to the regulatory subunits of PKA, it leads to the dissociation and activation of PKA, which allows the catalytic subunit of PKA to phosphorylate target proteins, thereby regulating various physiological functions and metabolic processes in cellular function. Recent researches also implicate the involvement of cAMP-PKA signaling in the pathologenesis of anxiety disorder. However, there are still debates on the prevention and treatment of anxiety disorders from this signaling pathway. To review the function of cAMP-PKA signaling in anxiety disorder, we searched the publications with the keywords including "cAMP", "PKA" and "Anxiety" from Pubmed, Embase, Web of Science and CNKI databases. The results showed that the number of publications on cAMP-PKA pathway in anxiety disorder tended to increase. Bioinformatics results displayed a close association between the cAMP-PKA pathway and the occurrence of anxiety. Mechanistically, cAMP-PKA signaling could influence brain-derived neurotrophic factor and neuropeptide Y and participate in the regulation of anxiety. cAMP-PKA signaling could also oppose the dysfunctions of gamma-aminobutyric acid (GABA), intestinal flora, hypothalamic-pituitary-adrenal axis, neuroinflammation, and signaling proteins (MAPK and AMPK) in anxiety. In addition, chemical agents with the ability to activate cAMP-PKA signaling demonstrated therapy potential against anxiety disorders. This review emphasizes the central roles of cAMP-PKA signaling in anxiety and the targets of the cAMP-PKA pathway would be potential candidates for treatment of anxiety. Nevertheless, more laboratory investigations to improve the therapeutic effect and reduce the adverse effect, and continuous clinical research will warrant the drug development.
环磷酸腺苷（cAMP）是一种细胞内的第二信使，由腺苷酸环化酶（AC）催化三磷酸腺苷转化而来。蛋白激酶 A（PKA）是 cAMP 的主要效应物，是一种由两个催化亚基和两个调节亚基组成的二聚体蛋白激酶。当 cAMP 与 PKA 的调节亚基结合时，会导致 PKA 的解离和激活，从而允许 PKA 的催化亚基磷酸化靶蛋白，从而调节细胞功能中的各种生理功能和代谢过程。最近的研究还表明，cAMP-PKA 信号通路参与了焦虑症的发病机制。然而，对于该信号通路在焦虑症的防治方面仍存在争议。为了综述 cAMP-PKA 信号通路在焦虑症中的作用，我们使用关键词“cAMP”、“PKA”和“Anxiety”在 Pubmed、Embase、Web of Science 和 CNKI 数据库中检索了相关文献。结果显示，有关焦虑症中 cAMP-PKA 通路的研究呈逐渐增多的趋势。生物信息学结果显示，cAMP-PKA 通路与焦虑症的发生密切相关。从机制上讲，cAMP-PKA 信号可以影响脑源性神经营养因子和神经肽 Y，并参与焦虑的调节。cAMP-PKA 信号还可以拮抗 γ-氨基丁酸（GABA）、肠道菌群、下丘脑-垂体-肾上腺轴、神经炎症和信号蛋白（MAPK 和 AMPK）的功能障碍。此外，具有激活 cAMP-PKA 信号能力的化学剂对焦虑症具有治疗潜力。本综述强调了 cAMP-PKA 信号在焦虑症中的核心作用，cAMP-PKA 通路的靶点将是治疗焦虑症的潜在候选药物。然而，还需要更多的实验室研究来提高治疗效果，降低不良反应，并进行持续的临床研究，以推动药物研发。
