Roles of necroptosis in alcoholic liver disease and hepatic pathogenesis

Chronic alcohol consumption can cause alcoholic liver disease (ALD), leading to morbidity and mortality worldwide. Complex disease progression of ALD varies from alcoholic fatty liver to alcoholic steatohepatitis, eventually contributing to fibrosis and cirrhosis. Accumulating evidence revealed that necroptosis, a way of programmed cell death different from apoptosis and traditional necrosis, is involved in the underlying pathogenic molecular mechanism of ALD. Receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed-lineage kinase domain-like pseudokinase have been implicated as key mediators to execute necroptosis. Also, necroptosis has gained increasing attention due to its potential association with primary pathological hallmarks of ALD, including oxidative stress, hepatic steatosis and inflammation. This review summarizes the recent progress on the roles and mechanisms of necroptosis and focuses on the crosstalk between necroptosis and the other pathogenesis of ALD, providing a theoretical basis for targeting necroptosis as a novel treatment for ALD.