Oxysterols: Old Tale, New Twists

Abstract

Oxysterols have long been known for their important role in cholesterol homeostasis, where they are involved in both transcriptional and posttranscriptional mechanisms for controlling cholesterol levels. However, they are increasingly associated with a wide variety of other, sometimes surprising cell functions. They are activators of the Hedgehog pathway (important in embryogenesis), and they act as ligands for a growing list of receptors, including some that are of importance to the immune system. Oxysterols have also been implicated in several diseases such as neurodegenerative diseases and atherosclerosis. Here, we explore the latest research into the roles oxy-sterols play in different areas, and we evaluate the current evidence for these roles. In addition, we outline critical concepts to consider when investigating the roles of oxysterols in various situations, which includes ensuring that the concentration and form of the oxysterol are relevant in that context--a caveat with which many studies have struggled.

Necroptosis-like Neuronal Cell Death Caused by Cellular Cholesterol Accumulation

“…Excessive cholesterol uptake/synthesis often results in the production of oxysterols, oxidized derivatives of cholesterol that are involved in the regulation of cholesterol homeostasis as well as the mediation of adverse outcomes of impaired cholesterol homeostasis (40). 24(S)-Hydroxycholesterol, which is produced in the CNS and effluxed from the CNS across the bloodbrain barrier due to its high hydrophobicity, is believed to be involved not only in the reduction of cholesterol levels in the CNS, but also in the mediation of adverse side effects (41).…”

LXR Regulation of Brain Cholesterol: From Development to Disease

“…Decreased levels of 27-OHC have been observed in several neurodegenerative disorders including AD, HD, and PD [15]. 27-OHC may link high peripheral cholesterol with many CNS diseases through its ability to upregulate the brain renin-angiotensin system in an LXR-dependent manner [16].…”

25‐Hydroxycholesterol protects against acute lung injury via targeting MD‐2

“…Oxysterols, oxidized forms of cholesterol, participate in cholesterol homeostasis, immune response and pathogenesis of several diseases such as neurodegenerative diseases and atherosclerosis . 25‐hydroxycholesterol (25HC), one of the oxysterols, has recently garnered much attention as a potential regulator of innate immunity and inflammation .…”

“…15 Oxysterols, oxidized forms of cholesterol, participate in cholesterol homeostasis, immune response and pathogenesis of several diseases such as neurodegenerative diseases and atherosclerosis. 16 25-hydroxycholesterol (25HC), one of the oxysterols, has recently garnered much attention as a potential regulator of innate immunity and inflammation. 17 Previous studies have demonstrated 25HC possesses antiviral effects against various viruses, including vesicular stomatitis virus (VSV), human immunodeficiency virus (HIV), Ebola virus (EBOV) and Zika virus (ZIKV) through inhibition of viral entry.…”