Neuro-Oxysterols and Neuro-Sterols as Ligands to Nuclear Receptors, G
Protein-Coupled Receptors, Ligand-Gated Ion Channels and other Protein
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 directly, 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 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, oxysterols and other sterols interact
with a variety of different receptors, including nuclear receptors e.g.
liver X receptors; membrane bound G protein-coupled receptors e.g.
smoothened; the endoplasmic reticulum resident proteins e.g. INSIG
(insulin induced gene), or the cholesterol sensing protein SCAP (SREBP
cleavage activating protein); and the ligand-gated ion channel
N-methyl-D-aspartate receptors found in nerve cells. In this review we
summaries the different oxysterols (neuro-oxysterol) and sterols
(neuro-sterols) found in the central nervous system whose biological
activity is transmitted via these different classes of protein