Roles of bile acids signaling in neuromodulation under physiological and pathological conditions

Cell & Bioscience

Review

Chen Xing¹  Xin Huang¹  Haoran Cui¹  Lung Song²  Shaojun Hou²  Dongxue Wang³  Dengjun Yu³ 

[1] Beijing Institute of Basic Medical Sciences, Taiping Road #27, 100850, Beijing, China;Beijing Institute of Basic Medical Sciences, Taiping Road #27, 100850, Beijing, China;Anhui Medical University, 230032, Heifei, China;Beijing Institute of Basic Medical Sciences, Taiping Road #27, 100850, Beijing, China;College of Pharmacy, Jiamusi University, 154007, Jiamusi, China;

关键词: Bile acids;    Cholesterol;    Blood brain barrier;    FXR;    TGR5;    Neurodegenerative diseases;    UDCA;    TUDCA;   

DOI  :  10.1186/s13578-023-01053-z

 received in 2023-02-24, accepted in 2023-05-13,  发布年份 2023

来源: Springer

【 摘 要 】

Bile acids (BA) are important physiological molecules not only mediating nutrients absorption and metabolism in peripheral tissues, but exerting neuromodulation effect in the central nerve system (CNS). The catabolism of cholesterol to BA occurs predominantly in the liver by the classical and alternative pathways, or in the brain initiated by the neuronal-specific enzyme CYP46A1 mediated pathway. Circulating BA could cross the blood brain barrier (BBB) and reach the CNS through passive diffusion or BA transporters. Brain BA might trigger direct signal through activating membrane and nucleus receptors or affecting activation of neurotransmitter receptors. Peripheral BA may also provide the indirect signal to the CNS via farnesoid X receptor (FXR) dependent fibroblast growth factor 15/19 (FGF15/19) pathway or takeda G protein coupled receptor 5 (TGR5) dependent glucagon-like peptide-1 (GLP-1) pathway. Under pathological conditions, alterations in BA metabolites have been discovered as potential pathogenic contributors in multiple neurological disorders. Attractively, hydrophilic ursodeoxycholic acid (UDCA), especially tauroursodeoxycholic acid (TUDCA) can exert neuroprotective roles by attenuating neuroinflammation, apoptosis, oxidative or endoplasmic reticulum stress, which provides promising therapeutic effects for treatment of neurological diseases. This review summarizes recent findings highlighting the metabolism, crosstalk between brain and periphery, and neurological functions of BA to elucidate the important role of BA signaling in the brain under both physiological and pathological conditions.

【 授权许可】

CC BY   
© The Author(s) 2023

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