PRESS RELEASE FROM THE EMBO JOURNAL
This press release is copyrighted to The EMBO Journal.
Brain cholesterol metabolism and Alzheimer's disease
The EMBO Journal advance online publication, 12 January 2006;
DOI: 10.1038/sj.emboj.7600398
Regulating cholesterol levels in the brain decreases levels of the
Amyloid-beta peptide, according to research published this week by The EMBO
journal. This peptide is thought to be the causative agent of involved in
the pathology of Alzheimer's disease.
In the study, by Hasan Mohajeri and colleagues, experiments performed in the
mouse brain show for the first time in vivo that interfering with the
activity of an enzyme required for the cholesterol production, seladin-1,
leads to an increase in Amyloid-beta formation. Conversely, the authors show
that increasing seladin-1 levels in cultured human neuroblastoma cells
reduces Amyloid-beta levels.
In the normal situation, special cholesterol-rich territories of the
membrane physically separate the precursor of Amyloid-beta peptide from the
enzymes that are necessary for the generation of the peptide. In the absence
of selanin-1, cholesterol levels are low and these territories are
disorganized, leaving the enzymes free to process the precursor of
Amyloid-beta peptide and form more of the toxic product.
Recent studies have implicated cholesterol metabolism in the pathophysiology
of Alzheimer's disease. The mechanism by which cholesterol modulates the
production of the toxic beta-amyloid peptide has however so far remained
elusive.
This study nicely confirms that seladin-1 play a crucial role in
Amyloid-beta peptide production in vivo, and indicates that pharmacological
enhancement of seladin-1 activity may be a novel therapeutic strategy for
Alzheimer's disease.
Author contacts:
Hasan Mohajeri (University of Zurich, Zurich, Switzerland)
Tel +41 634 88 72, E-mail: [email protected]
Lola Ledesma, (Cavalieri Ottolenghi Scientific Institute, Turin, Italy)
Tel +39 011 670 54 82, E-mail: [email protected]
Editorial contact:
Dr Valerie Ferrier, The EMBO Journal
Tel + 49 6221 88 91 403, E-mail: [email protected]
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