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Research from Rensselaer Polytechnic Institute professor offers clues to Alzheimer's disease
Date:6/24/2010

Troy, N.Y. An organic compound found in red wine resveratrol has the ability to neutralize the toxic effects of proteins linked to Alzheimer's disease, according to research led by Rensselaer Professor Peter M. Tessier. The findings, published in the May 28 edition of the Journal of Biological Chemistry, are a step toward understanding the large-scale death of brain cells seen in certain neurodegenerative diseases.

"We've shown how resveratrol has very interesting selectivity to target and neutralize a select set of toxic peptide isoforms," Tessier said. "Because resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms."

Isoforms are different packing arrangements of a particular peptide. Deformations of a particular peptide - the Aβ1-42 peptide - have been linked to Alzheimer's disease. Improperly folded peptides have been shown to collect in accumulations called "plaques" within the brain. Those plaques are often found near areas of cell death in diseased brains.

It is not clear that resveratrol is able to cross the blood-brain barrier, Tessier said. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging.

In their research, Tessier and his co-authors generated A peptides packed together in five unique isoforms, or "arrangements" (monomer, soluble oligomer, non-toxic oligomer, fibrillar intermediates and amyloid fibrils). In their experiments, three of these arrangements were toxic to human cells, two were not.

Next, the researchers introduced resveratrol.

The resveratrol reacted with the toxic arrangements of the Aβ1-42 peptide, neutralizing their toxicity.

It did not affect the non-toxic arrangements.

"The surprise is that this molecule can target some of these packing arrangements tha
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Contact: Mary Martialay
martim12@rpi.edu
518-276-2156
Rensselaer Polytechnic Institute
Source:Eurekalert

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