Description
24(S)-
hydroxy Cholesterol is a side-
chain substituted oxysterol that has important roles in cholesterol homeostasis. It is generated by the action of CYP46 on cholesterol in the brain and diffuses across the blood-
brain barrier to the systemic circulation where it can modulate cell signaling, be used for further sterol biosynthesis, or be metabolized in the liver. 24(S)-
hydroxy cholesterol potently activates LXRα and LXRβ nuclear receptors (EC
50 = 4 and 3 μM, respectively), causing upregulation of cholesterol-
lowering genes. In the brain, this oxysterol controls cholesterol processing to facilitate neurological repair during Alzheimer’s disease and other neuropathological conditions.
Uses
(3β,24S)-Cholest-5-ene-3,24-diol is used as a biomarker in the analysis of disease.
Uses
(3β,24S)-Cholest-5-ene-3,24-diol is used as a biomarker in the analysis of disease.
Definition
ChEBI: (24S)-24-hydroxycholesterol is a 24-hydroxycholesterol that has S configuration at position 24. It is the major metabolic breakdown product of cholesterol in the brain. It has a role as a mouse metabolite, a biomarker and a human blood serum metabolite.
General Description
24(S)-hydroxycholesterol (24HC) is synthesized from cholesterol in brain dendrites by the action of enzyme cholesterol 24-hydroxylase (CYP46A1). It is catabolized to bile acids in the liver.
Biochem/physiol Actions
24(S)-hydroxycholesterol (24HC) elevated levels are reported in liver inflammation and fibrosis. It is a N-methyl-D-aspartate receptor (NMDAR) modulator. The levels of 24HC are potential indicators of brain development as well as pathology including Alzheimer′s disease (AD) and multiple sclerosis. Polymorphism in the cholesterol 24-hydroxylase (CYP46A1) gene leads to elevated 24HC levels and toxicity. 24HC is a mediator of apoptosis and necroptosis. Elevated levels of 24HC are reported in liver inflammation and fibrosis.
References
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10.1073/pnas.93.18.9799[2] AJAY CHAWLA. Nuclear Receptors and Lipid Physiology: Opening the X-Files[J]. Science, 2001, 294 5548. DOI:
10.1126/science.294.5548.1866[3] HEIKE KÖLSCH . The neurotoxic effect of 24-hydroxycholesterol on SH-SY5Y human neuroblastoma cells[J]. Brain Research, 1999, 818 1: Pages 171-175. DOI:
10.1016/s0006-8993(98)01274-8[4] KAZUNORI YAMANAKA. 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis.[J]. The Journal of Biological Chemistry, 2011: 24666-24673. DOI:
10.1074/jbc.m111.236273[5] A second class of nuclear receptors for oxysterols: regulation of RORalpha and RORgamma activity by 24(S)-hydroxycholesteraol (cerebrosterol)
[6] VALERIO LEONI Claudio C. Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid[J]. Biochemical pharmacology, 2013, 86 1: Pages 26-36. DOI:
10.1016/j.bcp.2013.03.015[7] YASUOMI URANO Noriko N Sachika Ochiai. Suppression of amyloid-β production by 24S-hydroxycholesterol via inhibition of intracellular amyloid precursor protein trafficking[J]. FASEB Journal, 2013, 27 10: 4305-4315. DOI:
10.1096/fj.13-231456
