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New protein structure could help treat Alzheimer's, related diseases
Date:7/28/2014

esent usually isn't done until after death, in an autopsy.

As a result, many dementias are broadly diagnosed as Alzheimer's disease without definitive proof, and other diseases can go undiagnosed and untreated.

The molecular structure of an amyloid protein can be only slightly different from a normal protein and can transform to a toxic state fairly easily, which is why amyloid diseases are so prevalent. The researchers built a protein structure, called "alpha sheet," that complements the toxic structure of amyloid proteins that they discovered in computer simulations. The alpha sheet effectively attacks the toxic middle state the protein goes through as it transitions from normal to abnormal.

The structures could be tailored even further to bind specifically with the proteins in certain diseases, which could be useful for specific therapies. The researchers hope their designed compounds could be used as diagnostics for amyloid diseases and as drugs to treat the diseases or at least slow progression.

"For example, patients could have a broad first-pass test done to see if they have an amyloid disease and then drill down further to determine which proteins are present to identify the specific disease," Daggett said.

The research team includes Gene Hopping, Jackson Kellock and James Bryers of UW bioengineering; Gabriele Varani and Ravi Pratap Barnwal of UW chemistry; Peter Law, a former UW graduate student; and Byron Caughey of the National Institutes of Health's Rocky Mountain Laboratories. Working with the UW's Center for Commercialization, they have a patent on one compound and have submitted an application to patent the entire class of related compounds.

This research began a decade ago in Daggett's lab when a former graduate student, Roger Armen, first discovered this new secondary structure through computer simulations. Daggett's team was able to prove its validity in recent years by designing stable co
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Contact: Michelle Ma
mcma@uw.edu
206-543-2580
University of Washington
Source:Eurekalert  

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