Overexpressing SIKE1 for MASH

Overexpressing SIKE1, a cytosolic suppressor of interferon signaling, could help treat metabolic dysfunction-associated steatohepatitis (MASH), also known as NASH, by preventing interactions between the serine-threonine kinase TAK1 and its activator TAB2, and subsequent MAPK activation associated with metabolic dysfunction-associated steatotic liver (MAFL)-to-MASH progression.

Transcriptomic analysis of liver samples from humans, macaques, and mice, followed by functional and evolutionary conservation analyses, identified MAPK activation as a key driver of MAFL-to-MASH progression, and SIKE1 as a candidate negative regulator of that process. ...