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Last Updated: Apr 24, 2008 - 1:59:27 PM |
TURSDAY April 24, 2008 (foodconsumer.org) -- German scientists published a paper in the April 25, 2008 issue of Science saying that Alzheimer's disease may be treated by targeting discrete sub-compartments in the cell membrane (RAFTS).
RAFTS play an important role in complex physiological processes, such as the immune response and in many pathological situations.
In the case of Alzheimer's disease, ß-secretase in the cell membrane mediates production of ß-amyloid peptide, which is known to be linked to the disease.
The enzyme is involved in the conversion of cholesterol to ß-amyloid peptide. And high levels of cholesterol are correlated with increased production of the amyloid peptide, thus increasing odds of developing Alzheimer's.
The scientists who work for JADO Technologies GmbH described in the paper how the rate limiting enzyme in the production of Alzheimer's disease-associated with ß-amyloid peptide can be inhibited effectively using compounds anchored to the cell membrane RAFTS.
"Our data provide proof-of principle of a new approach for directing small molecule inhibitors to disease causing RAFT targets in cellular membranes," noted Professor Kai Simons, Max-Planck Institute of Molecular Cell Biology and Genetics and co-founder of JADO.
"By directing inhibition to the sub-compartment where the enzyme is active, the approach has potential to be used in the design of more effective β-secretase inhibitors for the treatment of Alzheimer's disease."
The new approach used a sterol anchor molecule to assist the inhibitor compounds to completely suppress the activity of ß-secretase, which is "internalized from the cell membrane into intracellular compartments (endosomes) where it cleaves its substrate, Amyloid Precursor Protein (APP)."
In an animal model of Alzheimer's disease, the same sterol-coupled inhibitor lowered production of ß-amyloid in the brain by 50 percent in 4 hours while the inhibitor alone was ineffective.
The sterol anchor helped target and increase the level of the inhibitor in the sterol-rich RAFTs where ß-secretase cleaves APP, according to the researchers.
In another study, Sebastien Hebert and colleagues of the Flanders Institute for Biotechnology, who are affiliated with Katholieke Universiteit – Leuven, found patients with the most common form of Alzheimer's disease had high levels of ß-secretase and lower levels of miR-29a and miR-29b-1.
The observation, according to the researchers, suggested a possible role of certain miRNA's in the increase of ß-secretase and in the formation of plagues in the brains of patients with Alzheimer's disease. If this proves to be true, the miRNA may serve as targets for developing anti-Alzheimer's drugs in the future.
The study titled Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/ß-secretase expression appears in the journal Proceedings of the National Academy of Sciences.
Alzheimer’s disease is the most common form of dementia found in the West. The disease is an incurable neurodegenerative disease that slowly and gradually destroys brain cells, a process that initially starts with the parts of the brain that control thought, memory and language.
The age-related disease affects an estimated 4.5 millions Americans. No one knows for sure what causes Alzheimer's disease, according to the U.S. government, although studies linked cholesterol to the increased risk of the disease.
© 2004-2008 by foodconsumer.org unless otherwise specified
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