New CRC publication in Liver International:
Alpha-1 Antitrypsin Inclusions Sequester GRP78 in a Bile Acid-Inducible Manner
Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder that results in the accumulation of misfolded AAT protein in liver cells, causing chronic liver injury. Principal investigators (PIs) Prof. Pavel Strnad and Dr. Nurdan Guldiken from project A03, in collaboration with project A07 (Olde Damink/Schaap) and researchers from Germany and France, systematically analyzed AAT aggregates to uncover their molecular composition. They identified GRP78, a key ER chaperone, as a major non-AAT protein trapped within these inclusions. Using PiZ mouse models and human liver/serum samples, the team demonstrated that bile acids drive GRP78 sequestration, exacerbating liver damage. These findings reveal a bile acid-mediated mechanism contributing to AATD-related liver disease and offer new directions for developing targeted therapies within the gut-liver axis framework.