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Published on: August 14, 2016
Oxysterols and neurodegenerative diseases
Ingemar Björkhem1, Angel Cedazo-Minguez, Valerio Leoni
1Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden. ingemar.bjorkhem@karolinska.se
Molecular Aspects of Medicine
|March 3, 2009
Summary
Cholesterol metabolites, 24S-hydroxycholesterol (24S-OHC) and 27-hydroxycholesterol (27-OHC), cross the blood-brain barrier. Altered 27-OHC flux into the brain may link hypercholesterolemia to Alzheimer
Area of Science:
- Neuroscience
- Biochemistry
- Metabolomics
Background:
- Cholesterol metabolites, 24S-hydroxycholesterol (24S-OHC) and 27-hydroxycholesterol (27-OHC), exhibit distinct blood-brain barrier (BBB) permeability.
- 24S-OHC facilitates cholesterol elimination from the brain, while 27-OHC enters the brain from circulation.
- The balance of these oxysterols may influence beta-amyloid peptide generation and neurodegenerative processes.
Purpose of the Study:
- To investigate the role of 27-hydroxycholesterol (27-OHC) flux in Alzheimer's disease (AD) pathogenesis.
- To explore the potential link between hypercholesterolemia and AD via 27-OHC.
- To discuss oxysterols as potential diagnostic markers for neurodegenerative diseases.
Main Methods:
- In vitro experiments.
- Primary cultures of rat hippocampal cells.
- Analysis of gene expression, specifically focusing on the Activity Regulated Cytoskeleton-associated protein (Arc).
Main Results:
- 27-hydroxycholesterol (27-OHC) suppressed the expression of Activity Regulated Cytoskeleton-associated protein (Arc) in rat hippocampal cells.
- Arc protein is crucial for memory consolidation and is reduced in Alzheimer's disease (AD) patients.
- The study posits that 27-OHC influx may represent a link between hypercholesterolemia and AD.
Conclusions:
- The flux of 27-hydroxycholesterol (27-OHC) into the brain may be a critical factor in Alzheimer's disease (AD) development.
- Modulating 27-OHC circulation could be a potential therapeutic strategy for AD.
- Oxysterols show promise as diagnostic biomarkers for neurodegenerative conditions.
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