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

Björkhem, I., Cedazo-Minguez, A., Leoni, V., Meaney, S. (2009). Oxysterols and neurodegenerative diseases. MOLECULAR ASPECTS OF MEDICINE, 30(3), 171-179 [10.1016/j.mam.2009.02.001].

Oxysterols and neurodegenerative diseases

Leoni V;
2009

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
Articolo in rivista - Review Essay
oxysterols, sterols, cholesterol, mass spectrometry, metabolomics, neurodegenerative diseases
English
2009
30
3
171
179
reserved
Björkhem, I., Cedazo-Minguez, A., Leoni, V., Meaney, S. (2009). Oxysterols and neurodegenerative diseases. MOLECULAR ASPECTS OF MEDICINE, 30(3), 171-179 [10.1016/j.mam.2009.02.001].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/221825
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