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September 14, 2005
German Scientists suggest sorting protein-related receptor (sorLa) protects against developing Alzheimer's
A hallmark of Alzheimer disease are protein plaques in the brain which accumulate over many years. They are derived from the amyloid precursor protein (APP) which for unknown reasons is chopped up into smaller fragments, including the amyloid beta peptide, which forms these dangerous plaques. The plaques destroy the patients' nerve cells and lead to dementia, impairing the patients memory, thinking, and behaviour. According to the National Institutes of Health (NIH) more than four million Americans suffer from AD, an incurable disease. The older one gets, the greater the risk of developing this disease. It is estimated that about half of the individuals over 85 years of age are affected.
Professor Willnow and his colleagues were able to demonstrate that the molecule, named sorLa (abb. sorting protein-related receptor), binds to APP in nerve cells and thus prevents its dissection into the amyloid beta peptide. They could also show that genetically modified mice which cannot produce sorLA have increased levels of amyloid beta peptides because APP is destructed at a much higher rate than in healthy animals.
The researchers also looked at the brains of patients who died from AD and compared them with subjects who had not suffered from this disease. Surprisingly, the nerve cells of the AD patients had not produced sorLA, but the nerve cells of the control group had done so. The researchers conclude that in individuals whose brains produce little or no sorLA, the uncontrolled production of amyloid beta peptides likely accelerates onset and progression of neurodegenerative processes, making sorLA an important risk factor for AD.
Ongoing research is directed towards identification of substances that could increase the production of sorLA in the brain of those people that produce insufficient amounts of the molecule. The researchers hope that in the future it will be possible to pharmacologically reduce the formation of these dangerous plaques in the brain by modulating sorLA levels.
*Neuronal sorting protein-rtelated receptor sorLA/LR11 regulates processingof the amyloid precursor protein. Olav M. Andersen*, Juliane Reiche*, Vanessa Schmidt*, Michael Gotthardt*, Robert Spoelgen*, Joachim Behlke*, Christine A. F. von Arnim?, Tilman Breiderhoff*, Pernille Jansen?, Xin Wu$, Kelly R. Bales§, Roberto Cappai, Colin L. Masters, Jørgen Gliemann?, Elliot J. Mufson?, Bradley T. Hyman?, Steven M. Paul§, Anders Nykjær?, and Thomas Willnow*,**
*Max Delbrueck Center for Molecular Medicine, 13125 Berlin-Buch, Germany; ?Massachusetts General Hospital, Charlestown, MA 02129; §Lilly Research Laboratories, Indianapolis, IN ooo; ?Department of Neurological Sciences, Rush University Medical Center, Chicago, IL ooo; ?Institute of Medical Biochemistry, University of Aarhus, DK-800, Denmark; and Mental Health Research Institute of Victoria, Parkville ooo, Australia
Press and Public Affairs: Max Delbrück Center for Molecular Medicine(MDC) Berlin-Buch
Barbara Bachtler Robert-Rössle-Str. 10 13125 Berlin bachtler@mdc-berlin.de , http://www.mdc-berlin.de
Source: idw-online.de (last viewed 12 September 2005) [FullText]
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