Abstract
In contrast to their parent molecule cholesterol, two of its side-chain oxidized metabolites are able to cross the blood-brain barrier. There is a concentration-driven flux of 24S-hydroxycholesterol (24S-OHC) from the brain into the circulation, which is of major importance for elimination of excess cholesterol from the brain. The opposite flux of 27-hydroxycholesterol (27-OHC) from the circulation into the brain may regulate a number of key enzymes within the brain. In vitro experiments suggest that the balance between the levels of these two molecules may be of importance for the generation of β-amyloid peptides. In primary cultures of rat hippocampal cells 27-OHC is able to suppress expression of the activity regulated cytoskeleton-associated protein (Arc), a protein important in memory consolidation which is reduced in patients with Alzheimer's disease (AD). In the present work we explore the possibility that the flux of 27-OHC from the circulation into the brain represents the missing link between AD and hypercholesterolemia, and discuss the possibility that modification of this flux may be a therapeutic strategy. Lastly, we discuss the use of oxysterols as diagnostic markers in neurodegenerative disease.
Original language | English |
---|---|
Pages (from-to) | 171-179 |
Number of pages | 9 |
Journal | Molecular Aspects of Medicine |
Volume | 30 |
Issue number | 3 |
DOIs | |
Publication status | Published - Jun 2009 |
Keywords
- β-Amyloid
- 24S-Hydroxycholesterol
- 27-Hydroxycholesterol
- Activity regulated cytoskeleton-associated protein
- Blood-brain barrier
- CYP27
- CYP46
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Molecular Medicine
- Clinical Biochemistry
- Medicine(all)