Neuro-oxysterols and neuro-sterols as ligands to nuclear receptors, GPCRs, ligand-gated ion channels and other protein receptors

摘要

The brain is the most cholesterol rich organ in the body containing about 25% of the body's free cholesterol. Cholesterol cannot pass the blood-brain barrier and be imported or exported; instead, it is synthesised in situ and metabolised to oxysterols, oxidised forms of cholesterol, which can pass the blood-brain barrier. 24S-Hydroxycholesterol is the dominant oxysterol in the brain after parturition, but during development, a myriad of other oxysterols are produced, which persist as minor oxysterols after birth. During both development and in later life, sterols and oxysterols interact with a variety of different receptors, including nuclear receptors, membrane bound GPCRs, the oxysterol/sterol sensing proteins INSIG and SCAP, and the ligand-gated ion channel NMDA receptors found in nerve cells. In this review, we summarise the different oxysterols and sterols found in the CNS whose biological activity is transmitted via these different classes of protein receptors.