Intrahepatic cholestasis is the main feature of a group of liver diseases that are characterized by hepatic and systemic accumulation of bile acids due to impaired excretion of bile, based on inflammation of intrahepatic and extrahepatic bile ducts or dysfunction of hepatobiliary transport proteins. The nuclear bile acid sensor farnesoid X receptor (FXR) is central for the regulation of bile acid turnover, including synthesis, hepatic excretion and intestinal and hepatic uptake. Several drugs targeting FXR have been developed for the treatment of cholestatic liver diseases, and so far one of them has been granted conditional approval. In this review, we will discuss the current knowledge and the clinical and experimental data available on agents affecting FXR and bile acid turnover.
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February 2022
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The highly conserved enzyme IMPDH plays an essential role in purine biosynthesis and is tightly regulated by many different mechanisms. Depicted here are cryo-EM structures of the large retinal splice variant of IMPDH1 in different filament assembly conformations overlaid on a cryo-EM micrograph of IMPDH1 filaments. Cover artwork created by Jesse Hansen.
Review Article|
February 22 2022
Bile acid metabolism and FXR-mediated effects in human cholestatic liver disorders
Antonio Molinaro;
Antonio Molinaro
1Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
2Department of Molecular and Clinical Medicine/Wallenberg Laboratory, University of Gothenburg, 413 45 Gothenburg, Sweden
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Hanns-Ulrich Marschall
1Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
2Department of Molecular and Clinical Medicine/Wallenberg Laboratory, University of Gothenburg, 413 45 Gothenburg, Sweden
Correspondence: Hanns-Ulrich Marschall (hanns-ulrich.marschall@gu.se)
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Publisher: Portland Press Ltd
Received:
December 16 2021
Revision Received:
January 28 2022
Accepted:
February 07 2022
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem Soc Trans (2022) 50 (1): 361–373.
Article history
Received:
December 16 2021
Revision Received:
January 28 2022
Accepted:
February 07 2022
Citation
Antonio Molinaro, Hanns-Ulrich Marschall; Bile acid metabolism and FXR-mediated effects in human cholestatic liver disorders. Biochem Soc Trans 28 February 2022; 50 (1): 361–373. doi: https://doi.org/10.1042/BST20210658
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