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20S-Hydroxycholesterol

20S-Hydroxycholesterol is a steroid of the oxysterol class. It is a human metabolite of cholesterol.

20S-Hydroxycholesterol has been the subject of research into its role in human health. For example, 20S-hydroxycholesterol has been found to be an allosteric activator of the Hedgehog signaling pathway, which has implications in cancer research.[1][2][3][4][5]

More recently, 20S-hydroxycholesterol was identified as an endogenous ligand for the sigma-2 receptor, which had previously been considered an orphan receptor since its discovery in 1990.[6][7]

References

  1. ^ Griffiths, William J.; Wang, Yuqin (2019). "Oxysterol research: A brief review". Biochemical Society Transactions. 47 (2): 517–526. doi:10.1042/BST20180135. PMC 6490702. PMID 30936243.
  2. ^ Kim, W. K.; Meliton, V.; Amantea, C. M.; Hahn, T. J.; Parhami, F. (2007). "20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism". Journal of Bone and Mineral Research. 22 (11): 1711–1719. doi:10.1359/jbmr.070710. PMID 17638575. S2CID 935824.
  3. ^ Nachtergaele, S.; Mydock, L. K.; Krishnan, K.; Rammohan, J.; Schlesinger, P. H.; Covey, D. F.; Rohatgi, R. (2012). "Oxysterols are allosteric activators of the oncoprotein Smoothened". Nature Chemical Biology. 8 (2): 211–220. doi:10.1038/nchembio.765. PMC 3262054. PMID 22231273.
  4. ^ Dwyer, J. R.; Sever, N.; Carlson, M.; Nelson, S. F.; Beachy, P. A.; Parhami, F. (2007). "Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells". The Journal of Biological Chemistry. 282 (12): 8959–8968. doi:10.1074/jbc.M611741200. PMID 17200122.
  5. ^ Nedelcu, D.; Liu, J.; Xu, Y.; Jao, C.; Salic, A. (2013). "Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling". Nature Chemical Biology. 9 (9): 557–564. doi:10.1038/nchembio.1290. PMC 3749252. PMID 23831757.
  6. ^ Derek Lowe (November 22, 2021). "Another Orphan Reunited". In The Pipeline. Science.
  7. ^ Cheng, Yu-Shiuan; Zhang, Tianyi; Ma, Xiang; Pratuangtham, Sarida; Zhang, Grace C.; Ondrus, Alexander A.; Mafi, Amirhossein; Lomenick, Brett; Jones, Jeffrey J.; Ondrus, Alison E. (2021). "A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes". Nature Chemical Biology. 17 (12): 1271–1280. doi:10.1038/s41589-021-00907-2. ISSN 1552-4450. PMC 8607797. PMID 34799735.