Oxysterols and Cellular Stress Responses
Summary
Oxysterols are oxygenated derivatives of cholesterol that arise through enzymatic and non-enzymatic pathways and act as bioactive lipids modulating myriad cellular processes. They influence membrane fluidity and serve as ligands for nuclear and membrane receptors, thereby regulating gene expression, lipid homeostasis and innate immunity. Central among their activities is the capacity to trigger and regulate stress-response pathways, including endoplasmic reticulum (ER) stress, autophagy, oxidative and nitrosative stress, and inflammatory signalling cascades. Through engagement of sensors such as unfolded protein response (UPR) mediators, toll-like receptors and liver X receptors, oxysterols orchestrate adaptive programmes that determine cell fate, balancing survival and death. Dysregulation of oxysterol levels or signalling contributes to pathologies as diverse as atherosclerosis, neurodegeneration, cancer progression and pregnancy disorders. Understanding the interplay between oxysterols and cellular stress responses offers avenues for biomarker development and therapeutic intervention, for instance via dietary modification, antioxidant strategies or receptor-targeted drugs.
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Oxysterols and Cellular Stress Responses publication trend
The graph below shows the total number of articles in oxysterols and cellular stress responses across all publications each year (not limited to Nature Index journals).
Technical terms
Oxysterols: Oxygenated derivatives of cholesterol that regulate lipid metabolism, membrane properties and signalling pathways.
Endoplasmic reticulum stress (ER stress): A cellular condition in which misfolded proteins accumulate in the ER, triggering the unfolded protein response.
Autophagy: A regulated process by which cells degrade and recycle damaged organelles and macromolecules to maintain homeostasis.
Nitrosative stress: Cellular damage caused by excessive reactive nitrogen species, often leading to protein modifications and signalling disruptions.
Liver X receptor (LXR): A nuclear receptor family that senses oxysterols and controls genes involved in cholesterol efflux and inflammation.
References
- When nitrosative stress hits the endoplasmic reticulum: Possible implications in oxLDL/oxysterols-induced endothelial dysfunction. Free Radical Biology and Medicine (2023).
- Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation. Marine Drugs (2024).
- Liver X Receptor Activation Attenuates Oxysterol-Induced Inflammatory Responses in Fetoplacental Endothelial Cells. Cells (2023).
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