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Review
. 2021 Aug;178(16):3176-3193.
doi: 10.1111/bph.15191. Epub 2020 Aug 7.

Neuro-oxysterols and neuro-sterols as ligands to nuclear receptors, GPCRs, ligand-gated ion channels and other protein receptors

Yuqin Wang  1 , Eylan Yutuc  1 , William J Griffiths  1
Affiliations
Free article
Review

Neuro-oxysterols and neuro-sterols as ligands to nuclear receptors, GPCRs, ligand-gated ion channels and other protein receptors

Yuqin Wang et al. Br J Pharmacol. 2021 Aug.
Free article

Abstract

The brain is the most cholesterol rich organ in the body containing about 25% of the body's free cholesterol. Cholesterol cannot pass the blood-brain barrier and be imported or exported; instead, it is synthesised in situ and metabolised to oxysterols, oxidised forms of cholesterol, which can pass the blood-brain barrier. 24S-Hydroxycholesterol is the dominant oxysterol in the brain after parturition, but during development, a myriad of other oxysterols are produced, which persist as minor oxysterols after birth. During both development and in later life, sterols and oxysterols interact with a variety of different receptors, including nuclear receptors, membrane bound GPCRs, the oxysterol/sterol sensing proteins INSIG and SCAP, and the ligand-gated ion channel NMDA receptors found in nerve cells. In this review, we summarise the different oxysterols and sterols found in the CNS whose biological activity is transmitted via these different classes of protein receptors. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.

Keywords: 24S,25-epoxycholesterol; 24S-hydroxycholesterol; G protein-coupled receptor; brain; cholesterol; nuclear receptor; oxysterol.

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References

REFERENCES

    1. Abdel-Khalik, J., Crick, P. J., Yutuc, E., DeBarber, A. E., Duell, P. B., Steiner, R. D., … Griffiths, W. J. (2018). Identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in human cerebrospinal fluid and plasma. Biochimie, 153, 86-98. https://doi.org/10.1016/j.biochi.2018.06.020
    1. Axelson, M., Larsson, O., Zhang, J., Shoda, J., & Sjovall, J. (1995). Structural specificity in the suppression of HMG-CoA reductase in human fibroblasts by intermediates in bile acid biosynthesis. Journal of Lipid Research, 36, 290-298.
    1. Alexander, S. P. H., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., & CGTP Collaborators (2019). The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology, 176(S1), S21-S141.
    1. Alexander, S. P. H., Mathie, A, Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., & CGTP Collaborators. (2019). The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology, 176(S1), S142-228.
    1. Bauman, D. R., Bitmansour, A. D., McDonald, J. G., Thompson, B. M., Liang, G., & Russell, D. W. (2009). 25-Hydroxycholesterol secreted by macrophages in response to toll-like receptor activation suppresses immunoglobulin A production. Proceedings of the National Academy of Sciences of the United States of America, 106, 16764-16769.

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