Ribosome collisions and ZAKα activation: explores the therapeutic potential of metabolic diseases.

Metabolic diseases such as diabetes, hypertension, and fatty liver, driven by obesity, are increasing due to overnutrition and physical inactivity. In these conditions, the ribosomal stress response (RSR) represents a previously underexplored mechanism. Dysregulated production of reactive oxygen species from sources including NADPH oxidase and the mitochondrial electron transport chain leads to oxidative stress, which can induce ribosome collisions. This, in turn, activates ZAKα and the RSR pathway, driving metabolic dysfunction through stress-activated kinases such as c-Jun N-terminal kinase and p38. Elucidating the interplay between reactive oxygen species, ribosomal stress, and metabolic disease could open new therapeutic avenues. Dietary interventions, including polyunsaturated fatty acids and natural antioxidants, have the potential to reduce oxidative stress and improve metabolic health. The aim of this review is to highlight the link between ROS and ribosomal stress, with a focus on targeting ribosome collisions as a therapeutic strategy in metabolic disorders. Future studies should also establish reliable biomarkers of aberrant oxidative stress to guide clinical interventions for metabolic disease.