24S-Hydroxycholesterol

24S-Hydroxycholesterol (24S-HC), also known as cholest-5-ene-3,24-diol or cerebrosterol, is an endogenous oxysterol produced by neurons in the brain to maintain cholesterol homeostasis.^[1] It was discovered in 1953 by Alberto Ercoli, S. Di Frisco, and Pietro de Ruggieri, who first isolated the molecule in the horse brain^[2] and then demonstrated its presence in the human brain.^[3]

24S-Hydroxycholesterol

Names
IUPAC name (24S)-Cholest-5-ene-3β,24-diol
Systematic IUPAC name (1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R,5S)-5-Hydroxy-6-methylheptan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol
Other names cerebrosterol
Identifiers
CAS Number	474-73-7
3D model (JSmol)	Interactive image
Beilstein Reference	3218472
ChEBI	CHEBI:34310
ChEMBL	ChEMBL171804
ChemSpider	108790
KEGG	C13550
PubChem CID	121948
UNII	47IMW63S3F
CompTox Dashboard (EPA)	DTXSID101313419
InChI InChI=1S/C27H46O2/c1-17(2)25(29)11-6-18(3)22-9-10-23-21-8-7-19-16-20(28)12-14-26(19,4)24(21)13-15-27(22,23)5/h7,17-18,20-25,28-29H,6,8-16H2,1-5H3/t18-,20+,21+,22-,23+,24+,25+,26+,27-/m1/s1 Key: IOWMKBFJCNLRTC-XWXSNNQWSA-N
SMILES C[C@H](CC[C@@H](C(C)C)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
Properties
Chemical formula	C27H46O2
Molar mass	402.663 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Structure

24S-HC is produced by a hydroxy group substitution at carbon number 24 in cholesterol, catalyzed by the enzyme cholesterol 24-hydroxylase (CYP46A1).^[4]

Production of 24S-hydroxycholesterol from cholesterol, as catalyzed by CYP46A1.

Function

24S-HC binds to apolipoproteins such as apoE, apoJ, and apoA1 to form HDL-like complexes^[5] which can cross the blood–brain barrier more easily than free cholesterol. Thus, 24S-HC production serves as one of several counterbalancing mechanisms for cholesterol synthesis in the brain.^[1][6] After entering general blood circulation and traveling to the liver, 24S-HC can be sulfated, glucuronidated, or converted into bile acids, which can ultimately be excreted.^[7]

24S-HC is an agonist of liver X receptors, a class of nuclear receptors that sense oxysterols. In the brain, liver X receptor beta is the primary LXR type, which interacts with 24S-HC.^[5] 24S-HC levels sensed by LXRs can regulate the expression of SREBP mRNA and protein, which in turn regulate cholesterol synthesis and fatty acid synthesis.^[8]

24S-HC may participate in several aspects of brain development and function, such as axon and dendrite growth or synaptogenesis,^[4] as well as acting as a positive allosteric modulator of NMDA receptors.^[9] Regulation of 24S-HC metabolism in neurons may play a role in their health and function, as well as their response to injury or disease.^[10] Blood plasma levels of 24S-HC may be altered after acute brain injuries such as stroke^[11] or in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and multiple sclerosis.^[12][13]