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胆汁酸信号在神经退行性和神经疾病中的作用。

Bile Acid Signaling in Neurodegenerative and Neurological Disorders.

机构信息

Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.

Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Int J Mol Sci. 2020 Aug 20;21(17):5982. doi: 10.3390/ijms21175982.

Abstract

Bile acids are commonly known as digestive agents for lipids. The mechanisms of bile acids in the gastrointestinal track during normal physiological conditions as well as hepatic and cholestatic diseases have been well studied. Bile acids additionally serve as ligands for signaling molecules such as nuclear receptor Farnesoid X receptor and membrane-bound receptors, Takeda G-protein-coupled bile acid receptor and sphingosine-1-phosphate receptor 2. Recent studies have shown that bile acid signaling may also have a prevalent role in the central nervous system. Some bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, have shown neuroprotective potential in experimental animal models and clinical studies of many neurological conditions. Alterations in bile acid metabolism have been discovered as potential biomarkers for prognosis tools as well as the expression of various bile acid receptors in multiple neurological ailments. This review explores the findings of recent studies highlighting bile acid-mediated therapies and bile acid-mediated signaling and the roles they play in neurodegenerative and neurological diseases.

摘要

胆汁酸通常被称为脂质的消化剂。在正常生理条件下以及在肝和胆汁淤积性疾病中,胆汁酸在胃肠道中的作用机制已得到充分研究。胆汁酸还可以作为信号分子的配体,如核受体法尼醇 X 受体和膜结合受体、Takeda G 蛋白偶联胆汁酸受体和鞘氨醇 1-磷酸受体 2。最近的研究表明,胆汁酸信号也可能在中枢神经系统中发挥重要作用。一些胆汁酸,如牛磺熊脱氧胆酸和熊去氧胆酸,在许多神经疾病的实验动物模型和临床研究中显示出神经保护潜力。已经发现胆汁酸代谢的改变可能是预后工具的潜在生物标志物,以及各种胆汁酸受体在多种神经疾病中的表达。本综述探讨了最近的研究结果,强调了胆汁酸介导的治疗方法和胆汁酸介导的信号转导,以及它们在神经退行性和神经疾病中的作用。

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