Author: Yifan Li1,2, Shufan Ding1, Yongjie Wang3
Affiliation: <sup>1</sup> School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
<sup>2</sup> School of Medicine, Hangzhou Normal University, Hangzhou, 311121, China.
<sup>3</sup> School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. wangyongjie@hznu.edu.cn.
Conference/Journal: Mol Biol Rep
Date published: 2025 Feb 4
Other:
Volume ID: 52 , Issue ID: 1 , Pages: 199 , Special Notes: doi: 10.1007/s11033-025-10288-7. , Word Count: 244
The cholinergic anti-inflammatory pathway (CAP) is comprised of the vagus nerve, acetylcholine, nicotinic acetylcholine receptors, the spleen, and the splenic nerve. It represents a sophisticated neuroimmune axis that critically regulates the crosstalk between the nervous system and the immune response via the vagus nerve. Here, we provided a nuanced exploration of the CAP's role in curbing inflammatory processes and its broad therapeutic potential across a spectrum of diseases. We meticulously dissect the intricate mechanisms by which the CAP modulates key signaling cascades, including the NF-κB, JAK2/STAT3, MAPK/ERK, PI3K/AKT, COX2/PGE2, and NRF2/HO-1 pathways, which are quintessential in the pathogenesis of various conditions. Additionally, we also summarized the CAP's profound implications in the management of inflammatory diseases, neurodegenerative disorders, metabolic syndromes, and oncological malignancies, elucidating its capacity to mitigate disease severity and progression through sophisticated immune modulation. The modulation of the CAP is suggested as a novel strategy that could potentially transform treatment approaches for a variety of conditions. However, the precise cellular and molecular underpinnings of the CAP's effects, as well as its translatability to clinical settings, remain subjects of ongoing investigation. The review calls for further research to demystify the mechanisms of the CAP and to harness its therapeutic potential fully, with the aim of developing innovative and efficacious treatment modalities that exploit the pathway's unique attributes.
Keywords: Alpha7Nachr; Cholinergic anti-inflammatory pathway; Inflammatory diseases; Signaling pathways; Splenic nerves; Vagus nerve.
PMID: 39903351 DOI: 10.1007/s11033-025-10288-7