文献类型：期刊文献

英文题名：The NO-cGMP signaling pathway and depression: mechanisms and therapeutic prospects

作者：Pi, Wenling[1];Sun, Yuting[1];Dai, Xueling[1];Huo, Qing[1];Zuo, Zeping[2];Xie, Fei[1];Sun, Yaxuan[1]

第一作者：Pi, Wenling

通讯作者：Xie, F[1];Sun, YX[1]

机构：[1]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Food, Beijing, Peoples R China;[2]Beijing Tongrentang Res Inst, Beijing, Peoples R China

第一机构：北京联合大学应用文理学院|北京联合大学生物化学工程学院

通讯机构：[1]corresponding author), Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Food, Beijing, Peoples R China.|[114172]北京联合大学应用文理学院;[11417]北京联合大学;[1141726]北京联合大学生物化学工程学院;

年份：2026

卷号：53

期号：1

外文期刊名：MOLECULAR BIOLOGY REPORTS

收录：;Scopus(收录号：2-s2.0-105047520032);WOS:【SCI-EXPANDED(收录号:WOS:001851694500010)】；

基金：The authors declare that financial support was received for the research, authorship, and/or publication of this article.This research was supported by the State Administration for Market Regulation Science and Technology Plan Project, No. 2023MK215; National Science and Technology Major Project, No. 2014ZX09301307;National Natural Science Foundation of China, No. 11975048 the Academic Research Projects of Beijing Union University, No. ZK10202204 Education Reform Project of Beijing Union University, No. JY2023Y008.

语种：英文

外文关键词：Depression; NO-cGMP signaling pathway; Soluble guanylate cyclase; Phosphodiesterase inhibitor; Neuralplasticity

摘要：Depression is a highly prevalent and serious mental disorder affecting populations worldwide. However, the traditional monoamine hypothesis does not fully account for its pathogenesis. In recent years, considerable attention has been directed toward the role of the NO-cGMP signaling pathway in the pathophysiology and treatment of depression.Nitric oxide (NO), a gaseous neurotransmitter, activates soluble guanylate cyclase (sGC), thereby increasing the level of the second messenger cyclic guanosine monophosphate (cGMP). In turn, this regulation modulates protein kinase G (PKG) and its downstream signaling cascades. This pathway has been implicated in synaptic plasticity, neurogenesis, and inflammatory responses.Substantial evidence indicates that abnormalities in the NO-cGMP pathway-observed both in patients with depression and in animal models-manifest as elevated NO levels, decreased cGMP content, and altered activities of related enzymes. These changes are thought to interact with multiple other signaling systems to jointly contribute to depressive pathophysiology.A variety of antidepressant drugs and natural products (e.g., vitamin C, pyridoxine, curcumin) have been shown to exert antidepressant effects through modulation of this pathway. Therapeutic strategies targeting this pathway-including NO donors, sGC activators, and phosphodiesterase (PDE) inhibitors-exhibit therapeutic potential.The present review comprehensively summarizes the molecular mechanisms of the NO-cGMP signaling pathway, its role in the pathogenesis of depression, and targeted treatment strategies, with the aim of providing a theoretical foundation for the development of novel antidepressants.