Deng Fengcheng, Yang Dan, Qing Lingxi, Chen Yifei, Zou Jilian, Jia Meiling, Wang Qian, Jiang Runda, Huang Lihua
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.
Neural Regen Res. 2025 Nov 1;20(11):3095-3112. doi: 10.4103/NRR.NRR-D-24-00607. Epub 2024 Nov 13.
The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
肠道微生物群与宿主中枢神经系统中环状单磷酸腺苷(cAMP)-蛋白激酶A(PKA)信号通路之间的相互作用在神经疾病中起着关键作用,并增强了沿肠-脑轴的通讯。肠道微生物群通过其代谢产物影响cAMP-PKA信号通路,这些代谢产物激活迷走神经并调节免疫和神经内分泌系统。相反,cAMP-PKA信号通路的改变会影响肠道微生物群的组成,形成一个微生物-宿主相互作用的动态网络。这种相互调节影响神经发育、神经递质控制和行为特征,从而在神经疾病的调节中发挥作用。肠道微生物群和cAMP-PKA信号通路的协同活动调节诸如淀粉样β蛋白聚集、线粒体功能障碍、异常能量代谢、小胶质细胞激活、氧化应激和神经递质释放等过程,这些过程共同影响神经疾病的发生和发展。本研究探讨了肠道微生物群与cAMP-PKA信号通路之间的复杂相互作用,及其对神经疾病潜在治疗干预的影响。最近的药理学研究表明,恢复肠道菌群与cAMP-PKA信号通路之间的平衡可能改善神经退行性疾病和情绪障碍的治疗效果。这可以通过多种方法实现,如饮食调整、益生菌补充剂、中药提取物、中药组合和创新剂型。这些发现表明,调节肠道微生物群和cAMP-PKA信号通路可能为开发神经退行性疾病的新型治疗方法提供有价值的证据。