Oxysterols are bioactive lipids formed from the oxidation of cholesterol.1 Once formed, oxysterols can induce the expression and synthesis of chemokines, inflammatory cytokines, and adhesion molecules, all of which can contribute to inflammatory responses.1 These inflammatory responses thus provide a link between oxysterols and disease pathogenesis.2
Studies have documented oxysterols as a contributor to a gamut of diseases, such as ￼atherosclerosis, Alzheimer’s disease, age-onset macular degeneration, cardiovascular diseases, diabetes, infertility, multiple sclerosis, Niemann-Pick disease type C, osteoporosis, Parkinson’s disease, and cancers.3 Oxysterol derangement can thus pose a danger to human health, and exploring oxysterols could offer new insights into disease etiology.
High levels of oxysterols can contribute to atherosclerosis, the buildup of plaque inside artery walls that decreases blood flow.4,5
A progressive neurologic disorder, Alzheimer’s disease results in lost memory and impaired mental function. Oxysterols have been implicated in the progression of Alzheimer’s disease through their regulation of cholesterol synthesis and modulation of inflammatory responses.6
Research documented a correlation of oxysterols to infertility based on data showing that infertile men have substantially higher levels of cholesterol in sperm membranes than fertile men.7 Thus, understanding the regulation of sterol synthesis offers an opportunity for research about male fertility.
Multiple sclerosis occurs when the immune system targets myelin, the insulating sheath around nerve fibers, resulting in nerve damage and deterioration, thus disrupting transmission of signals along nerve axons. Research has linked the oxysterol, 24-hydroxycholesterol, to multiple sclerosis and other neurodegenerative diseases.8
Osteoporosis, a skeletal disorder characterized by low bone mass, can be partially caused by inflammation, triggered by oxysterols.9
Cancer manifests when cells begin to grow uncontrollably. Oxysterols can influence tumor growth due to their immune modulating actions.10
Research Implications of Oxysterols
Leveraging oxysterols in research could drive the next wave of developing new therapies, diagnostic processes, and prediction methodologies for various diseases.
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1. Brzeska, M., Szymczyk, K., Szterk, A. Current Knowledge about Oxysterols: A Review. Journal of food science. 2016; 81: 2299-2308. DOI: https://doi.org/10.1111/1750-3841.13423
2. Poli G, Biasi F, Leonarduzzi G. Oxysterols in the pathogenesis of major chronic diseases. Redox Biol. 2013; 1(1): 125–30.
3. Samadi A, Sabuncuoglu S, Samadi M, Isikhan SY, Chirumbolo S, Peana M, Lay I, Yalcinkaya A, Bjørklund G. A Comprehensive Review on Oxysterols and Related Diseases. Curr Med Chem. 2021; 28(1): 110-136. doi: 10.2174/0929867327666200316142659.
4. Meynier A, Lherminier J, Demaison-Meloche J, Ginies C, Grandgirard A, Demaison L. Effects of dietary oxysterols on coronary arteries in hyperlipidaemic hamsters. Br J Nutr. 2002; 87(5): 447–58.
5. de Freitas FA, Levy D, Reichert CO, Cunha-Neto E, Kalil J, Bydlowski SP. Effects of Oxysterols on Immune Cells and Related Diseases. Cells. 2022; 11(8): 1251. https://doi.org/10.3390/cells11081251
6. Lathe, R.; Sapronova, A.; Kotelevtsev, Y. Atherosclerosis and alzheimer—Diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr. 2014; 14: 36.
7. Garolla, A.; Šabović, I.; Tescari, S.; De Toni, L.; Mene-gazzo, M.; Cosci, I.; De Filippis, V.; Giarola, M.; Foresta, C. Impaired sperm function in infertile men relies on the membrane sterol pattern. Andrology. 2018; 6(2): 325-334. http://dx.doi.org/10.1111/andr.12468 PMID: 29378089
8. Teunissen, C.E.; Dijkstra, C.D.; Polman, C.H.; Hoogervorst, E.L.; von Bergmann, K.; Lütjohann, D. Decreased levels of the brain specific 24s-hydroxycholesterol and cholesterol precursors in serum of multiple sclerosis patients. Neurosci Lett. 2003; 347: 159–162.
9. Zarrouk, A., Vejux, A., Mackrill, J., O’Callaghan, Y., Hammami, M., O’Brien, N., & Lizard, G. Involvement of oxysterols in age-related diseases and ageing processes. Ageing research reviews. 2014; 18: 148-162.
10. Traversari, C., Sozzani, S., Steffensen, K. R., & Russo, V. (2014). LXR‐dependent and‐independent effects of oxysterols on immunity and tumor growth. European journal of immunology. 2014; 44(7): 1896-1903.