Oxysterols in the pathogenesis of major chronic diseases

Pathological accumulation of 27-carbon intermediates or end-products of cholesterol metabolism, named oxysterols, may contribute to the onset and especially to the development of major chronic diseases in which inflammation, but also oxidative damage and to a certain extent cell death, are hallmarks and primary mechanisms of progression. Indeed, certain oxysterols exercise strong pro-oxidant and pro-inflammatory effects at concentrations detectable in the lesions typical of atherosclerosis, neurodegenerative diseases, inflammatory bowel diseases, age-related macular degeneration, and other pathological conditions characterized by altered cholesterol uptake and/or metabolism.
Graphical Abstract AAA Research highlights ► Oxysterols are 27-carbon-atom products of enzymatic or non-enzymatic oxidation of cholesterol. ► Oxidative stress is the major non-enzymatic source of oxysterols. ► Oxysterols may in turn amplify oxidative redox imbalance in cells and tissues. ► Pathological accumulation of oxysterols triggers and sustains inflammatory reactions. ► Oxysterol-mediated inflammation is a primary mechanism of progression in major chronic diseases.