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 (EC50 = 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.
