Cholesterol is an important plasma membrane component, precursor for hormones and vitamins, and is a regulator of metabolism. However, the oxidized forms of cholesterol (oxysterols) can cause toxicity and induce pro-inflammatory responses and are implicated in chronic degenerative diseases. In general, oxysterols with a modified sidechain serve in various physiological and/or pathophysiological functions. The source of these oxysterols may be exogenous, from the food we ingest, or endogenous, as the by-product of normal cholesterol metabolism, free radical-mediated oxidation, or autoxidation of cholesterol. This chapter discusses the nature of oxysterols as oxidized cholesterol species, oxysterol signaling and pathophysiology, oxysterols and neurodegenerative diseases, ozone-oxidized cholesterol as a new class of oxysterols, detection of 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (cholesterol secoaldehyde, ChSeco or atheronal-A) at sites of inflammation and evidence for in vivo existence, cytotoxicity of ChSeco and pro-inflammatory actions in the cells of mammalian systems, and ChSeco signaling in neuronal cells and implications in Alzheimer’s pathology.
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