24(S)-Hydroxycholesterol | Endogenous cholesterol metabolite

24(S)-Hydroxycholesterol (474-73-7) 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. 24S Hydroxycholesterol has also been found to be a high affinity ligand for RORα and RORγ (K_i = 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

References/Citations:

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 in plasma 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., 27 4305