Oxysterols: Old Tale, New Twists

Literature Cited

1. Kandutsch AA, Chen HW, Heiniger HJ. 1.  1978. Biological activity of some oxygenated sterols. Science 201:498–501 [Google Scholar]
2. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. 2.  1989. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N. Engl. J. Med. 320:915–24 [Google Scholar]
3. Brown AJ, Jessup W. 3.  1999. Oxysterols and atherosclerosis. Atherosclerosis 142:1–28 [Google Scholar]
4. Gill S, Chow R, Brown AJ. 4.  2008. Sterol regulators of cholesterol homeostasis and beyond: the oxysterol hypothesis revisited and revised. Prog. Lipid Res. 47:391–404 [Google Scholar]
5. Russell DW. 5.  2003. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72:137–74 [Google Scholar]
6. Mast N, Annalora AJ, Lodowski DT, Palczewski K, Stout CD, Pikuleva IA. 6.  2011. Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J. Biol. Chem. 286:5607–13 [Google Scholar]
7. Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. 7.  1998. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J. Lipid Res. 39:1594–600 [Google Scholar]
8. Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D. 8.  et al. 2011. Oxysterols direct immune cell migration via EBI2. Nature 475:524–27 [Google Scholar]
9. Nelson JA, Steckbeck SR, Spencer TA. 9.  1981. Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide. J. Biol. Chem. 256:1067–68 [Google Scholar]
10. Goyal S, Xiao Y, Porter NA, Xu L, Guengerich FP. 10.  2014. Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1. J. Lipid Res. 55:1933–43 [Google Scholar]
11. Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T. 11.  et al. 2011. Cholesterol 25-hydroxylation activity of CYP3A. J. Lipid Res. 52:1509–16 [Google Scholar]
12. Brown AJ, Jessup W. 12.  2009. Oxysterols: sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis. Mol. Asp. Med. 30:111–22 [Google Scholar]
13. Terao J. 13.  2014. Cholesterol hydroperoxides and their degradation mechanism. Subcell. Biochem. 77:83–91 [Google Scholar]
14. Brown AJ, Leong SL, Dean RT, Jessup W. 14.  1997. 7-Hydroperoxycholesterol and its products in oxidized low density lipoprotein and human atherosclerotic plaque. J. Lipid Res. 38:1730–45 [Google Scholar]
15. Shinkyo R, Xu L, Tallman KA, Cheng Q, Porter NA, Guengerich FP. 15.  2011. Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide intermediate. J. Biol. Chem. 286:33021–28 [Google Scholar]
16. Bjorkhem I, Diczfalusy U, Lovgren-Sandblom A, Starck L, Jonsson M. 16.  et al. 2014. On the formation of 7-ketocholesterol from 7-dehydrocholesterol in patients with CTX and SLO. J. Lipid Res. 55:1165–72 [Google Scholar]
17. Tempel W, Grabovec I, MacKenzie F, Dichenko YV, Usanov SA. 17.  et al. 2014. Structural characterization of human cholesterol 7α-hydroxylase. J. Lipid Res. 55:1925–32 [Google Scholar]
18. Larsson H, Bottiger Y, Iuliano L, Diczfalusy U. 18.  2007. In vivo interconversion of 7β-hydroxycholesterol and 7-ketocholesterol, potential surrogate markers for oxidative stress. Free Radic. Biol. Med. 43:695–701 [Google Scholar]
19. Mitic T, Shave S, Semjonous N, McNae I, Cobice DF. 19.  et al. 2013. 11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo. Biochem. Pharmacol. 86:146–53 [Google Scholar]
20. Diczfalusy U. 20.  2013. On the formation and possible biological role of 25-hydroxycholesterol. Biochimie 95:455–60 [Google Scholar]
21. Dzeletovic S, Babiker A, Lund E, Diczfalusy U. 21.  1995. Time course of oxysterol formation during in vitro oxidation of low density lipoprotein. Chem. Phys. Lipids 78:119–28 [Google Scholar]
22. Sanchez-Guijo A, Oji V, Hartmann MF, Schuppe HC, Traupe H, Wudy SA. 22.  2015. High levels of oxysterol sulfates in serum of patients with steroid sulfatase deficiency. J. Lipid Res. 56:403–12 [Google Scholar]
23. Ren S, Ning Y. 23.  2014. Sulfation of 25-hydroxycholesterol regulates lipid metabolism, inflammatory responses, and cell proliferation. Am. J. Physiol. Endocrinol. Metab. 306:E123–30 [Google Scholar]
24. Meng LJ, Griffiths WJ, Nazer H, Yang Y, Sjovall J. 24.  1997. High levels of (24S)-24-hydroxycholesterol 3-sulfate, 24-glucuronide in the serum and urine of children with severe cholestatic liver disease. J. Lipid Res. 38:926–34 [Google Scholar]
25. Lin CY, Morel DW. 25.  1996. Esterification of oxysterols in human serum: effects on distribution and cellular uptake. J. Lipid Res. 37:168–78 [Google Scholar]
26. Dzeletovic S, Breuer O, Lund E, Diczfalusy U. 26.  1995. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal. Biochem. 225:73–80 [Google Scholar]
27. Olkkonen VM, Li S. 27.  2013. Oxysterol-binding proteins: sterol and phosphoinositide sensors coordinating transport, signaling and metabolism. Prog. Lipid Res. 52:529–38 [Google Scholar]
28. Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M. 28.  et al. 2007. The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem. J. 405:473–80 [Google Scholar]
29. Weber-Boyvat M, Kentala H, Peranen J, Olkkonen VM. 29.  2014. Ligand-dependent localization and function of ORP-VAP complexes at membrane contact sites. Cell. Mol. Life Sci. 72:1967–87 [Google Scholar]
30. Hynynen R, Suchanek M, Spandl J, Back N, Thiele C, Olkkonen VM. 30.  2009. OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids. J. Lipid Res. 50:1305–15 [Google Scholar]
31. Charman M, Colbourne TR, Pietrangelo A, Kreplak L, Ridgway ND. 31.  2014. Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival. J. Biol. Chem. 289:15705–17 [Google Scholar]
32. Phillips MC. 32.  2014. Molecular mechanisms of cellular cholesterol efflux. J. Biol. Chem. 289:24020–29 [Google Scholar]
33. Terasaka N, Yu S, Yvan-Charvet L, Wang N, Mzhavia N. 33.  et al. 2008. ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet. J. Clin. Investig. 118:3701–13 [Google Scholar]
34. Wang N, Yvan-Charvet L, Lutjohann D, Mulder M, Vanmierlo T. 34.  et al. 2008. ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain. FASEB J. 22:1073–82 [Google Scholar]
35. Tarling EJ, Bojanic DD, Tangirala RK, Wang X, Lovgren-Sandblom A. 35.  et al. 2010. Impaired development of atherosclerosis in Abcg1^−/−Apoe^−/− mice: identification of specific oxysterols that both accumulate in Abcg1^−/−Apoe^−/− tissues and induce apoptosis. . Arterioscler. Thromb. Vasc. Biol. 30:1174–80 [Google Scholar]
36. Terasaka N, Wang N, Yvan-Charvet L, Tall AR. 36.  2007. High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1. PNAS 104:15093–98 [Google Scholar]
37. Peyrot SM, Nachtergaele S, Luchetti G, Mydock-McGrane LK, Fujiwara H. 37.  et al. 2014. Tracking the subcellular fate of 20(S)-hydroxycholesterol with click chemistry reveals a transport pathway to the Golgi. J. Biol. Chem. 289:11095–110 [Google Scholar]
38. Radhakrishnan A, Sun LP, Kwon HJ, Brown MS, Goldstein JL. 38.  2004. Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain. Mol. Cell 15:259–68 [Google Scholar]
39. Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL. 39.  2007. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig. PNAS 104:6511–18 [Google Scholar]
40. Gale SE, Westover EJ, Dudley N, Krishnan K, Merlin S. 40.  et al. 2009. Side chain oxygenated cholesterol regulates cellular cholesterol homeostasis through direct sterol-membrane interactions. J. Biol. Chem. 284:1755–64 [Google Scholar]
41. Kristiana I, Luu W, Stevenson J, Cartland S, Jessup W. 41.  et al. 2012. Cholesterol through the looking glass: ability of its enantiomer also to elicit homeostatic responses. J. Biol. Chem. 287:33897–904 [Google Scholar]
42. Olsen BN, Schlesinger PH, Baker NA. 42.  2009. Perturbations of membrane structure by cholesterol and cholesterol derivatives are determined by sterol orientation. J. Am. Chem. Soc. 131:4854–65 [Google Scholar]
43. Olsen BN, Schlesinger PH, Ory DS, Baker NA. 43.  2011. 25-Hydroxycholesterol increases the availability of cholesterol in phospholipid membranes. Biophys. J. 100:948–56 [Google Scholar]
44. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. 44.  1996. An oxysterol signalling pathway mediated by the nuclear receptor LXRα. Nature 383:728–31 [Google Scholar]
45. DeBose-Boyd RA. 45.  2008. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res. 18:609–21 [Google Scholar]
46. Gill S, Stevenson J, Kristiana I, Brown AJ. 46.  2011. Cholesterol-dependent degradation of squalene monooxygenase, a control point in cholesterol synthesis beyond HMG-CoA reductase. Cell Metab. 13:260–73 [Google Scholar]
47. Schroepfer GJ Jr. 47.  2000. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol. Rev. 80:361–554 [Google Scholar]
48. Zerenturk EJ, Kristiana I, Gill S, Brown AJ. 48.  2012. The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol synthesis at DHCR24 (Seladin-1). Biochim. Biophys. Acta 1821:1269–77 [Google Scholar]
49. Briscoe J, Therond PP. 49.  2013. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat. Rev. Mol. Cell Biol. 14:416–29 [Google Scholar]
50. Corcoran RB, Scott MP. 50.  2006. Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. PNAS 103:8408–13 [Google Scholar]
51. Dwyer JR, Sever N, Carlson M, Nelson SF, Beachy PA, Parhami F. 51.  2007. Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J. Biol. Chem. 282:8959–68 [Google Scholar]
52. Nachtergaele S, Mydock LK, Krishnan K, Rammohan J, Schlesinger PH. 52.  et al. 2012. Oxysterols are allosteric activators of the oncoprotein Smoothened. Nat. Chem. Biol. 8:211–20 [Google Scholar]
53. Rohatgi R, Milenkovic L, Scott MP. 53.  2007. Patched1 regulates Hedgehog signaling at the primary cilium. Science 317:372–76 [Google Scholar]
54. Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF. 54.  2005. Vertebrate Smoothened functions at the primary cilium. Nature 437:1018–21 [Google Scholar]
55. Nedelcu D, Liu J, Xu Y, Jao C, Salic A. 55.  2013. Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling. Nat. Chem. Biol. 9:557–64 [Google Scholar]
56. Nachtergaele S, Whalen DM, Mydock LK, Zhao Z, Malinauskas T. 56.  et al. 2013. Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling. eLife 2:e01340 [Google Scholar]
57. Myers BR, Sever N, Chong YC, Kim J, Belani JD. 57.  et al. 2013. Hedgehog pathway modulation by multiple lipid binding sites on the smoothened effector of signal response. Dev. Cell 26:346–57 [Google Scholar]
58. Wang C, Wu H, Katritch V, Han GW, Huang XP. 58.  et al. 2013. Structure of the human smoothened receptor bound to an antitumour agent. Nature 497:338–43 [Google Scholar]
59. Chen JK, Taipale J, Cooper MK, Beachy PA. 59.  2002. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16:2743–48 [Google Scholar]
60. Umetani M, Shaul PW. 60.  2011. 27-Hydroxycholesterol: the first identified endogenous SERM. Trends Endocrinol. Metab. 22:130–35 [Google Scholar]
61. DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP. 61.  2008. 27-Hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol. Endocrinol. 22:65–77 [Google Scholar]
62. Wu Q, Ishikawa T, Sirianni R, Tang H, McDonald JG. 62.  et al. 2013. 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep. 5:637–45 [Google Scholar]
63. DuSell CD, Nelson ER, Wang X, Abdo J, Modder UI. 63.  et al. 2010. The endogenous selective estrogen receptor modulator 27-hydroxycholesterol is a negative regulator of bone homeostasis. Endocrinology 151:3675–85 [Google Scholar]
64. Nelson ER, DuSell CD, Wang X, Howe MK, Evans G. 64.  et al. 2011. The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors. Endocrinology 152:4691–705 [Google Scholar]
65. Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL. 65.  et al. 2007. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat. Med. 13:1185–92 [Google Scholar]
66. Umetani M, Ghosh P, Ishikawa T, Umetani J, Ahmed M. 66.  et al. 2014. The cholesterol metabolite 27-hydroxycholesterol promotes atherosclerosis via proinflammatory processes mediated by estrogen receptor alpha. Cell Metab. 20:172–82 [Google Scholar]
67. Solt LA, Burris TP. 67.  2012. Action of RORs and their ligands in (patho)physiology. Trends Endocrinol. Metab. 23:619–27 [Google Scholar]
68. Wang Y, Kumar N, Solt LA, Richardson TI, Helvering LM. 68.  et al. 2010. Modulation of retinoic acid receptor-related orphan receptor α and γ activity by 7-oxygenated sterol ligands. J. Biol. Chem. 285:5013–25 [Google Scholar]
69. Wang Y, Kumar N, Crumbley C, Griffin PR, Burris TP. 69.  2010. A second class of nuclear receptors for oxysterols: regulation of RORα and RORγ activity by 24S-hydroxycholesterol (cerebrosterol). Biochim. Biophys. Acta 1801:917–23 [Google Scholar]
70. Jin L, Martynowski D, Zheng S, Wada T, Xie W, Li Y. 70.  2010. Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORγ. Mol. Endocrinol. 24:923–29 [Google Scholar]
71. Soroosh P, Wu J, Xue X, Song J, Sutton SW. 71.  et al. 2014. Oxysterols are agonist ligands of RORγt and drive Th17 cell differentiation. PNAS 111:12163–68 [Google Scholar]
72. Rauen T, Juang YT, Hedrich CM, Kis-Toth K, Tsokos GC. 72.  2012. A novel isoform of the orphan receptor RORγt suppresses IL-17 production in human T cells. Genes Immun. 13:346–50 [Google Scholar]
73. Santori FR, Huang P, van de Pavert SA, Douglass EF Jr, Leaver DJ. 73.  et al. 2015. Identification of natural RORγ ligands that regulate the development of lymphoid cells. Cell Metab. 21:286–97 [Google Scholar]
74. Liu C, Yang XV, Wu J, Kuei C, Mani NS. 74.  et al. 2011. Oxysterols direct B-cell migration through EBI2. Nature 475:519–23 [Google Scholar]
75. Raccosta L, Fontana R, Maggioni D, Lanterna C, Villablanca EJ. 75.  et al. 2013. The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils. J. Exp. Med. 210:1711–28 [Google Scholar]
76. Paul SM, Doherty JJ, Robichaud AJ, Belfort GM, Chow BY. 76.  et al. 2013. The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J. Neurosci. 33:17290–300 [Google Scholar]
77. Linsenbardt AJ, Taylor A, Emnett CM, Doherty JJ, Krishnan K. 77.  et al. 2014. Different oxysterols have opposing actions at N-methyl-D-aspartate receptors. Neuropharmacology 85:232–42 [Google Scholar]
78. Kim WK, Meliton V, Amantea CM, Hahn TJ, Parhami F. 78.  2007. 20(S)-Hydroxycholesterol inhibits PPARγ expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism. J. Bone Miner. Res. 22:1711–19 [Google Scholar]
79. Spann NJ, Glass CK. 79.  2013. Sterols and oxysterols in immune cell function. Nat. Immunol. 14:893–900 [Google Scholar]
80. Traversari C, Russo V. 80.  2012. Control of the immune system by oxysterols and cancer development. Curr. Opin. Pharmacol. 12:729–35 [Google Scholar]
81. Cyster JG, Dang EV, Reboldi A, Yi T. 81.  2014. 25-Hydroxycholesterols in innate and adaptive immunity. Nat. Rev. Immunol. 14:731–43 [Google Scholar]
82. McDonald JG, Russell DW. 82.  2010. Editorial: 25-Hydroxycholesterol: a new life in immunology. J. Leukoc. Biol. 88:1071–72 [Google Scholar]
83. Civra A, Cagno V, Donalisio M, Biasi F, Leonarduzzi G. 83.  et al. 2014. Inhibition of pathogenic non-enveloped viruses by 25-hydroxycholesterol and 27-hydroxycholesterol. Sci. Rep. 4:7487 [Google Scholar]
84. Bauman DR, Bitmansour AD, McDonald JG, Thompson BM, Liang G, Russell DW. 84.  2009. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production. PNAS 106:16764–69 [Google Scholar]
85. Diczfalusy U, Olofsson KE, Carlsson AM, Gong M, Golenbock DT. 85.  et al. 2009. Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. J. Lipid Res. 50:2258–64 [Google Scholar]
86. Park K, Scott AL. 86.  2010. Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons. J. Leukoc. Biol. 88:1081–87 [Google Scholar]
87. Gold ES, Diercks AH, Podolsky I, Podyminogin RL, Askovich PS. 87.  et al. 2014. 25-Hydroxycholesterol acts as an amplifier of inflammatory signaling. PNAS 111:10666–71 [Google Scholar]
88. Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG. 88.  2014. Inflammation. 25-Hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Science 345:679–84 [Google Scholar]
89. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA. 89.  et al. 2004. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119:299–309 [Google Scholar]
90. Korf H, Vander Beken S, Romano M, Steffensen KR, Stijlemans B. 90.  et al. 2009. Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice. J. Clin. Investig. 119:1626–37 [Google Scholar]
91. A-Gonzalez N, Bensinger SJ, Hong C, Beceiro S, Bradley MN. 91.  et al. 2009. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 31:245–58 [Google Scholar]
92. Yi T, Wang X, Kelly LM, An J, Xu Y. 92.  et al. 2012. Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses. Immunity 37:535–48 [Google Scholar]
93. Kelly LM, Pereira JP, Yi T, Xu Y, Cyster JG. 93.  2011. EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues. J. Immunol. 187:3026–32 [Google Scholar]
94. Yi T, Cyster JG. 94.  2013. EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture. eLife 2:e00757 [Google Scholar]
95. Gatto D, Wood K, Caminschi I, Murphy-Durland D, Schofield P. 95.  et al. 2013. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat. Immunol. 14:446–53 [Google Scholar]
96. Gatto D, Paus D, Basten A, Mackay CR, Brink R. 96.  2009. Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity 31:259–69 [Google Scholar]
97. Liu SY, Aliyari R, Chikere K, Li G, Marsden MD. 97.  et al. 2013. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38:92–105 [Google Scholar]
98. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T. 98.  et al. 2013. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38:106–18 [Google Scholar]
99. Arita M, Kojima H, Nagano T, Okabe T, Wakita T, Shimizu H. 99.  2013. Oxysterol-binding protein family I is the target of minor enviroxime-like compounds. J. Virol. 87:4252–60 [Google Scholar]
100. Porter FD, Scherrer DE, Lanier MH, Langmade SJ, Molugu V. 100.  et al. 2010. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci. Transl. Med. 2:56ra81 [Google Scholar]
101. York AG, Bensinger SJ. 101.  2013. Subverting sterols: rerouting an oxysterol-signaling pathway to promote tumor growth. J. Exp. Med. 210:1653–56 [Google Scholar]
102. Zarrouk A, Vejux A, Mackrill J, O'Callaghan Y, Hammami M. 102.  et al. 2014. Involvement of oxysterols in age-related diseases and ageing processes. Ageing Res. Rev. 18:148–62 [Google Scholar]
103. Bjorkhem I, Cedazo-Minguez A, Leoni V, Meaney S. 103.  2009. Oxysterols and neurodegenerative diseases. Mol. Asp. Med. 30:171–79 [Google Scholar]
104. Leoni V, Mariotti C, Tabrizi SJ, Valenza M, Wild EJ. 104.  et al. 2008. Plasma 24S-hydroxycholesterol and caudate MRI in pre-manifest and early Huntington's disease. Brain 131:2851–59 [Google Scholar]
105. Leoni V, Mariotti C, Nanetti L, Salvatore E, Squitieri F. 105.  et al. 2011. Whole body cholesterol metabolism is impaired in Huntington's disease. Neurosci. Lett. 494:245–49 [Google Scholar]
106. Leoni V, Long JD, Mills JA, Di Donato S, Paulsen JS. 106.  PREDICT-HD Study Group 2013. Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression. Neurobiol. Dis. 55:37–43 [Google Scholar]
107. Lutjohann D, Papassotiropoulos A, Bjorkhem I, Locatelli S, Bagli M. 107.  et al. 2000. Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J. Lipid Res. 41:195–98 [Google Scholar]
108. Mateos L, Ismail MA, Gil-Bea FJ, Leoni V, Winblad B. 108.  et al. 2011. Upregulation of brain renin angiotensin system by 27-hydroxycholesterol in Alzheimer's disease. J. Alzheimer's Dis. 24:669–79 [Google Scholar]
109. Teunissen CE, Lutjohann D, von Bergmann K, Verhey F, Vreeling F. 109.  et al. 2003. Combination of serum markers related to several mechanisms in Alzheimer's disease. Neurobiol. Aging 24:893–902 [Google Scholar]
110. Hughes TM, Kuller LH, Lopez OL, Becker JT, Evans RW. 110.  et al. 2012. Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease. J. Alzheimer's Dis. 30:53–61 [Google Scholar]
111. Solomon A, Leoni V, Kivipelto M, Besga A, Oksengard AR. 111.  et al. 2009. Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer's disease. Neurosci. Lett. 462:89–93 [Google Scholar]
112. Bretillon L, Siden A, Wahlund LO, Lutjohann D, Minthon L. 112.  et al. 2000. Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci. Lett. 293:87–90 [Google Scholar]
113. Kolsch H, Heun R, Kerksiek A, Bergmann KV, Maier W, Lutjohann D. 113.  2004. Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients. Neurosci. Lett. 368:303–8 [Google Scholar]
114. Zuliani G, Donnorso MP, Bosi C, Passaro A, Dalla Nora E. 114.  et al. 2011. Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study. BMC Neurol. 11:121 [Google Scholar]
115. Bjorkhem I, Andersson O, Diczfalusy U, Sevastik B, Xiu RJ. 115.  et al. 1994. Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages. PNAS 91:8592–96 [Google Scholar]
116. Sharpe LJ, Burns V, Brown AJ. 116.  2014. A lipidomic perspective on intermediates in cholesterol synthesis as indicators of disease status. J. Genet. Genomics 41:275–82 [Google Scholar]
117. Griffiths WJ, Crick PJ, Wang Y. 117.  2013. Methods for oxysterol analysis: past, present and future. Biochem. Pharmacol. 86:3–14 [Google Scholar]
118. Schott HF, Lutjohann D. 118.  2015. Validation of an isotope dilution gas chromatography-mass spectrometry method for combined analysis of oxysterols and oxyphytosterols in serum samples. Steroids 99:139–50 [Google Scholar]
119. Brown AJ, Mander EL, Gelissen IC, Kritharides L, Dean RT, Jessup W. 119.  2000. Cholesterol and oxysterol metabolism and subcellular distribution in macrophage foam cells. Accumulation of oxidized esters in lysosomes. J. Lipid Res. 41:226–37 [Google Scholar]
120. Farez MF, Quintana FJ, Gandhi R, Izquierdo G, Lucas M, Weiner HL. 120.  2009. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat. Immunol. 10:958–64 [Google Scholar]
121. Bjorkhem I, Diczfalusy U, Olsson T, Russell DW, McDonald JG. 121.  et al. 2011. Detecting oxysterols in the human circulation. Nat. Immunol. 12:577 [Google Scholar]
122. Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW. 122.  2003. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J. Biol. Chem. 278:22980–88 [Google Scholar]
123. Wong J, Quinn CM, Gelissen IC, Brown AJ. 123.  2008. Endogenous 24(S),25-epoxycholesterol fine-tunes acute control of cellular cholesterol homeostasis. J. Biol. Chem. 283:700–7 [Google Scholar]
124. Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW. 124.  2007. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 5:73–79 [Google Scholar]
125. Li-Hawkins J, Lund EG, Turley SD, Russell DW. 125.  2000. Disruption of the oxysterol 7α-hydroxylase gene in mice. J. Biol. Chem. 275:16536–42 [Google Scholar]
126. Stiles AR, McDonald JG, Bauman DR, Russell DW. 126.  2009. CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. J. Biol. Chem. 284:28485–89 [Google Scholar]
127. Omoto Y, Lathe R, Warner M, Gustafsson JA. 127.  2005. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice. PNAS 102:2814–19 [Google Scholar]
128. Chiang JYL, Kimmel R, Stroup D. 128.  2001. Regulation of cholesterol 7α-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXRα). Gene 262:257–65 [Google Scholar]
129. Meaney S, Hassan M, Sakinis A, Lutjohann D, von Bergmann K. 129.  et al. 2001. Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study. J. Lipid Res. 42:70–78 [Google Scholar]
130. Lorbek G, Lewinska M, Rozman D. 130.  2012. Cytochrome P450s in the synthesis of cholesterol and bile acids—from mouse models to human diseases. FEBS J. 279:1516–33 [Google Scholar]
131. Metcalfe C, de Sauvage FJ. 131.  2011. Hedgehog fights back: mechanisms of acquired resistance against Smoothened antagonists. Cancer Res. 71:5057–61 [Google Scholar]
132. Lichtenstein AH, Brecher P. 132.  1983. Esterification of cholesterol and 25-hydroxycholesterol by rat liver microsomes. Biochim. Biophys. Acta 751:340–48 [Google Scholar]
133. Szedlacsek SE, Wasowicz E, Hulea SA, Nishida HI, Kummerow FA, Nishida T. 133.  1995. Esterification of oxysterols by human plasma lecithin-cholesterol acyltransferase. J. Biol. Chem. 270:11812–19 [Google Scholar]
134. Ren S, Hylemon P, Zhang ZP, Rodriguez-Agudo D, Marques D. 134.  et al. 2006. Identification of a novel sulfonated oxysterol, 5-cholesten-3β,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria. J. Lipid Res. 47:1081–90 [Google Scholar]
135. Ren S, Kim JK, Kakiyama G, Rodriguez-Agudo D, Pandak WM. 135.  et al. 2014. Identification of novel regulatory cholesterol metabolite, 5-cholesten, 3β,25-diol, disulfate. PLOS ONE 9:e103621 [Google Scholar]
136. Hughes TM, Lopez OL, Evans RW, Kamboh MI, Williamson JD. 136.  et al. 2014. Markers of cholesterol transport are associated with amyloid deposition in the brain. Neurobiol. Aging 35:802–7 [Google Scholar]
137. Leoni V, Masterman T, Diczfalusy U, De Luca G, Hillert J, Bjorkhem I. 137.  2002. Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis. Neurosci. Lett. 331:163–66 [Google Scholar]
138. Teunissen CE, Dijkstra CD, Polman CH, Hoogervorst EL, von Bergmann K, Lutjohann D. 138.  2003. Decreased levels of the brain specific 24S-hydroxycholesterol and cholesterol precursors in serum of multiple sclerosis patients. Neurosci. Lett. 347:159–62 [Google Scholar]
139. Lee CY, Seet RC, Huang SH, Long LH, Halliwell B. 139.  2009. Different patterns of oxidized lipid products in plasma and urine of dengue fever, stroke, and Parkinson's disease patients: cautions in the use of biomarkers of oxidative stress. Antioxid. Redox Signal. 11:407–20 [Google Scholar]
140. Karrenbauer VD, Leoni V, Lim ET, Giovannoni G, Ingle GT. 140.  et al. 2006. Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis. Clin. Neurol. Neurosurg. 108:456–60 [Google Scholar]
141. van de Kraats C, Killestein J, Popescu V, Rijkers E, Vrenken H. 141.  et al. 2014. Oxysterols and cholesterol precursors correlate to magnetic resonance imaging measures of neurodegeneration in multiple sclerosis. Mult. Scler. 20:412–17 [Google Scholar]
142. Bjorkhem I, Lovgren-Sandblom A, Leoni V, Meaney S, Brodin L. 142.  et al. 2013. Oxysterols and Parkinson's disease: evidence that levels of 24S-hydroxycholesterol in cerebrospinal fluid correlates with the duration of the disease. Neurosci. Lett. 555:102–5 [Google Scholar]