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 |
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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)
Cite this
Oxysterols and neurodegenerative diseases. / Björkhem, Ingemar; Cedazo-Minguez, Angel; Leoni, Valerio; Meaney, Steve.
In: Molecular Aspects of Medicine, Vol. 30, No. 3, 06.2009, p. 171-179.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxysterols and neurodegenerative diseases
AU - Björkhem, Ingemar
AU - Cedazo-Minguez, Angel
AU - Leoni, Valerio
AU - Meaney, Steve
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - β-Amyloid
KW - 24S-Hydroxycholesterol
KW - 27-Hydroxycholesterol
KW - Activity regulated cytoskeleton-associated protein
KW - Blood-brain barrier
KW - CYP27
KW - CYP46
UR - http://www.scopus.com/inward/record.url?scp=67349094556&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349094556&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2009.02.001
DO - 10.1016/j.mam.2009.02.001
M3 - Article
C2 - 19248803
AN - SCOPUS:67349094556
VL - 30
SP - 171
EP - 179
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
IS - 3
ER -