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Neuro-Oxysterols and Neuro-Sterols as Ligands to Nuclear Receptors, G Protein-Coupled Receptors, Ligand-Gated Ion Channels and other Protein Receptors
  • Yuqin Wang,
  • Eylan Yutuc,
  • William GriffithsOrcid
Yuqin Wang
Swansea University
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Eylan Yutuc
Swansea University
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William Griffiths
Orcid
Swansea University
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Peer review status:ACCEPTED

16 Apr 2020Submitted to British Journal of Pharmacology
17 Apr 2020Submission Checks Completed
17 Apr 2020Assigned to Editor
17 Apr 2020Reviewer(s) Assigned
04 May 2020Editorial Decision: Revise Minor
19 May 20201st Revision Received
20 May 2020Submission Checks Completed
20 May 2020Assigned to Editor
20 May 2020Reviewer(s) Assigned
29 May 2020Editorial Decision: Revise Minor
16 Jun 20202nd Revision Received
18 Jun 2020Submission Checks Completed
18 Jun 2020Assigned to Editor
19 Jun 2020Review(s) Completed, Editorial Evaluation Pending
21 Jun 2020Editorial Decision: Accept

Abstract

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 receptors.