24(S)-Hydroxycholesterol
Endogenous cholesterol metabolite / 24(S)-Hydroxycholesterol is an important cholesterol metabolite (cholesterol 24-hydroxylase) found in the brain.1 It is an endogenous agonist of the nuclear receptor LXR.2 It has been shown to induce cell death in neuroblastoma cells3, possibly via a necroptosis pathway4. 24(S)-Hydroxycholesterol has also been found to be a high affinity ligand for RORα and RORγ (Ki = 25 nM).5 24(S)-Hydroxycholesterol levels are elevated in the cerebral spinal fluids of patients with neurogenerative diseases suggesting possible clinical applications.6,7 It was also able to reduce Aβ production and increase ER-resident immature amyloid precursor protein (APP) levels in human neuroblastoma SH-Sy5Y cells and CHO cells via inhibition of intracellular amyloid precursor protein trafficking.7
Biochemicals & reagents
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1) Lujohann et al. (1996), Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into circulation; Proc. Natl. Acad. Sci. USA, 93 9799 2) Chawla et al. (2001), Nuclear receptors and lipid physiology:opening the X-files; Science, 294 1866 3) Kolsch et al. (1999), The neurotoxic effect of 24-hydroxycholesterol on SH-SY5Y human neuroblastoma cells; Brain Res., 818 171 4) Yamanaka et al. (2011), 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis; J. Biol. Chem., 286 24666 5) Wang et al. (2010), A second class of nuclear receptors for oxysterols: regulation of RORalpha and RORgamma activity by 24(S)-hydroxycholesteraol (cerebrosterol); Biochim. Biophys. Acta, 1801 917 6) Leoni and Caccia (2013), Potential diagnostic applications of side chain oxysterols analysis inplasma and cerebrospinal fluid; Biochem. Pharmacol., 86 26 7) Urano et al. (2013), Suppression of amyloid-β production by 24S-hydroxycholesterol via inhibition of intracellular amyloid precursor protein trafficking; FASEB J., Jul 9 Epub.
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TARGET: Transcription factor -- PATHWAY: Cholesterol metabolism; Necroptosis; Transcription -- RESEARCH AREA: Neuroscience; Cell death; Stem cells -- DISEASE AREA: Neurodegeneration