Oxysterols and neurodegenerative diseases

Ingemar Björkhem, Angel Cedazo-Minguez, Valerio Leoni, Steve Meaney

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)171-179
Number of pages9
JournalMolecular Aspects of Medicine
Volume30
Issue number3
DOIs
Publication statusPublished - Jun 2009

Fingerprint

Neurodegenerative diseases
Neurodegenerative Diseases
Brain
Fluxes
Alzheimer Disease
Cholesterol
Molecules
Metabolites
Hypercholesterolemia
Blood-Brain Barrier
Cytoskeleton
Amyloid
Consolidation
Rats
Proteins
Oxysterols
Data storage equipment
Peptides
Enzymes
Experiments

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

Björkhem, I., Cedazo-Minguez, A., Leoni, V., & Meaney, S. (2009). Oxysterols and neurodegenerative diseases. Molecular Aspects of Medicine, 30(3), 171-179. https://doi.org/10.1016/j.mam.2009.02.001

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 journalArticle

Björkhem, I, Cedazo-Minguez, A, Leoni, V & Meaney, S 2009, 'Oxysterols and neurodegenerative diseases', Molecular Aspects of Medicine, vol. 30, no. 3, pp. 171-179. https://doi.org/10.1016/j.mam.2009.02.001
Björkhem I, Cedazo-Minguez A, Leoni V, Meaney S. Oxysterols and neurodegenerative diseases. Molecular Aspects of Medicine. 2009 Jun;30(3):171-179. https://doi.org/10.1016/j.mam.2009.02.001
Björkhem, Ingemar ; Cedazo-Minguez, Angel ; Leoni, Valerio ; Meaney, Steve. / Oxysterols and neurodegenerative diseases. In: Molecular Aspects of Medicine. 2009 ; Vol. 30, No. 3. pp. 171-179.
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