Ubiquitin-like posttranslational modifications in NAFLD progression and treatment

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a long-lasting condition that affects the liver, destroying its function. Liver injury can cause steatosis and inflammation, and further activation of hepatic stellate cells (HSCs) often leads to the development of nonalcoholic liver fibrosis. The patient with NAFLD is at risk of developing advanced liver disease and complications, such as liver failure, hepatocellular carcinoma (HCC), and portal hypertension. Although our understanding of the cellular and molecular mechanisms of NAFLD has greatly improved in recent years, treatment remains limited. Analysis and characterization of protein posttranslational modifications (PTMs) could improve our understanding of NAFLD pathology and leading to the development of new and more effective treatments. In recent years, a number of studies have described how ubiquitin-like (Ubl)-PTMs change during NAFLD and how treatments targeting specific enzymes mediating these Ubl-PTMs can improve various liver diseases, particularly in relation to NAFLD and nonalcoholic liver fibrosis. New strategies for evaluating modified proteomes could provide novel insights into the roles of Ubl-PTMs in NAFLD progression and the therapeutic value of targeting the proteins involved in these Ubl-PTMs.