A Comprehensive Review on Oxysterols and Related Diseases

Abstract

The present review aims at providing a complete and comprehensive summary of current literature relevant to oxysterols and related diseases. Oxidation of cholesterol leads to the formation of a large number of oxidation products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, steroid hormones, and 1,25-dihydroxyvitamin D3. Although oxysterols are considered as metabolic intermediates, there is a growing body of evidence that many oxysterols are bioactive, and their absence or excess may be part of the cause of a disease phenotype. These compounds derive from either enzymatic or non-enzymatic oxidation of cholesterol. This study provides comprehensive information about the structures, formation, and types of the oxysterols even when involved in certain disease states, focusing on their effects on metabolism and linkages with these diseases. The role of specific oxysterols as mediators in various disorders, such as degenerative (age-related) and cancer-related disorders, have now become clearer. Oxysterol levels may be employed as suitable markers for the diagnosis of specific diseases or in predicting the incidence rate of diseases, such as diabetes mellitus, Alzheimer’s disease, multiple sclerosis, osteoporosis, lung cancer, breast cancer, and infertility. However, further investigations may be required to confirm these mentioned debates.

Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells

“…Preventing the 7KC cytotoxicity by means of nutrients present in the Mediterranean diet (polyphenols, fatty acids) could be a means to counteract several diseases associated with oxidative stress leading to increased levels of 7KC mainly formed by cholesterol auto-oxidation [6,44]. In the present study, we showed that 7KC-induced cytotoxicity on murine neuronal N2a cells is characterized by ROS overproduction, alteration of plasma membrane, and drop of transmembrane mitochondrial potential (∆Ψm) leading to cell death.…”

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19

“…An increased prevalence of fungal and Pseudomonas aeruginosa colonization has also been observed in patients with severe forms of COVID-19, suggesting that this association may be the result of a failure in the regulation of immune defenses against pathogens other than SARS-CoV-2, in the case of co-infection [ 55 ]. From a clinical point of view, atherosclerosis, AMD, cataract, and Alzheimer's disease are age-related diseases [ 42 , 56 ]. At the beginning of the pandemic, COVID-19 could be considered as an emerging age-related disease.…”

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases

“…With increased lifespans in human populations, the number of age-related diseases (cardiovascular diseases, eye diseases (cataract), age-related macular degeneration (AMD or ARMD)), neurodegenerative diseases (Parkinson’s disease, dementias and Alzheimer’s disease (AD), certain cancers) increase [ 1 , 2 , 3 ]. As these diseases have an important societal and financial impact, it is imperative to find drugs to decrease their frequencies.…”