Wednesday, November 2, 2011

Genes identified as suppressors of Aβ toxicity
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In a development that sheds new light on the pathology of Alzheimer's disease (AD), a team of Whitehead Institute scientists has identified connections between genetic risk factors for the disease and the effects of a peptide toxic to nerve cells in the brains of AD patients. 

The scientists, working in and in collaboration with the lab of Whitehead Member Susan Lindquist, established these previously unknown links in an unexpected way. They used a very simple cell type - yeast cells - to investigate the harmful effects of amyloid beta (Aβ), a peptide whose accumulation in amyloid plaques is a hallmark of AD. This new yeast model of Aβ toxicity, which they further validated in the worm C. elegans and in rat neurons, enables researchers to identify and test potential genetic modifiers of this toxicity. 

"As we tackle other diseases and extend our lifetimes, Alzheimer's and related diseases will be the most devastating personal challenge for our families and one the most crushing burdens on our economy," says Lindquist, who is also a professor of biology at Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute. "We have to try new approaches and find out-of the-box solutions." 

In a multi-step process, the researchers were able to introduce the form of Aβ most closely associated with AD into yeast in a manner that mimics its presence in human cells. The resulting toxicity in yeast reflects aspects of the mechanism by which this protein damages neurons. This became clear when a screen of the yeast genome for genes that affect Aβ toxicity identified a dozen genes that have clear human homologs, including several that have previously been linked to AD risk by genome-wide association studies (GWAS) but with no known mechanistic connection. Continue to readmedilexicon.com

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