analysis of oxysterols to better understand their pathophysiological role

Omics Abstract High amounts of cholesterol have been definitely associated with the pathogenesis of several diseases, including metabolic and neurodegenerative disorders, cardiovascular diseases, and cancer. In all these pathologies the exacerbation of pro-oxidant and inflammatory responses is a consistent feature. In this scenario, species derived from enzymatic and non-enzymatic cholesterol oxidation, namely oxysterols, are strongly suspected to play a primary role. The consideration of these bioactive lipids is therefore helpful in investigating pathological mechanisms and may also acquire clinical value for the diagnosis and treatment of the disease. For this purpose and considering that a great number of oxysterols may be present together in the body, the employment of lipidomics technology certainly represents a powerful strategy for the simultaneous detection and characterization of these compounds in biological specimens. In this review we will discuss the applicability of lipidomics approach in the study of the association between oxysterols and diseases. Abstract High amounts of cholesterol have been definitely associated with the pathogenesis of several diseases, including metabolic and neurodegenerative disorders, cardiovascular diseases, and cancer. In all these pathologies the exacerbation of pro-oxidant and inflammatory responses is a consistent feature. In this scenario, species derived from enzymatic and non-enzymatic cholesterol oxidation, namely oxysterols, are strongly suspected to play a primary role. The consideration of these bioactive lipids is therefore helpful in investigating pathological mechanisms and may also acquire clinical value for the diagnosis and treatment of the disease. For this purpose and considering that a great number of oxysterols may be present together in the body, the employment of lipidomics technology certainly represents a powerful strategy for the simultaneous detection and characterization of these compounds in biological specimens. In this review we will discuss the applicability of lipidomics approach in the study of the association between oxysterols and diseases. 24-OH-7-DHC, 24-hydroxy-7-dehydrocholesterol; 24-OH-8-DHC, 24-hydroxy-8-dehydrocholesterol; 24S,25-EPOX, 24S,25-epoxycholesterol; 25-HC, 25-hydroxycholesterol; 25-OH-8-DHC, 25-hydroxy-8-dehydrocholesterol; 27-HC, 27-hydroxycholesterol; 27-OH-8-DHC, 27-hydroxy-8-dehydrocholesterol; Aβ, amyloid β; AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; AMD, age-related macular degeneration; APCI, atmospheric pressure chemical ionization; BC, breast cancer; BBB, blood-brain barrier; ChEH, cholesterol-5,6-epoxide hydrolase; CSF. cerebrospinal fluid; CVD, cardiovascular disease; CTX, cerebrotendinous xanthomatosis; CYP2αA1, sterol 27-hydroxylase; DHCEO, 3 β ,5 α -dihydroxycholest-7-en-6-one; ESI, electrospray ionization; HD, Huntington’s disease; LC, liquid chromatography; LXR, liver X receptor; GC, gas chromatography; HPLC, high-performance LC; IR, insulin resistance; MCI, mild cognitive impairment; MetS, metabolic syndrome; MRM, multiple reaction monitoring; MS, mass spectrometry; MS/MS, tandem mass spectrometry; MSdis, multiple sclerosis; MS n , multistage fragmentation; NAFLD, non-alcoholic fatty liver disease; NPC, Niemann-Pick type C disease; OCDO, 6-oxo-cholestan-3 β ,5 α -diol; PD, Parkinson’s disease; PDA, photodiode array; ROS, reactive oxygen species; SLO, Smith-Lemli-Opitz syndrome; SPE, solid phase extraction; TRIOL, cholestane-3β,5α,6β-triol;