New discovery may lead to improved drugs for Alzheimer's

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Washington, Aug 22 : Massachusetts Institute of Technology researchers have identified the structures of a protein key to Alzheimer's disease that may lead to development of new drugs.

Two kinds of proteins amyloid and tau are key to Alzheimer's disease.

With the help of new computer-based technique, researchers Collin M. Stultz, Associate Professor of Biomedical Engineering in the Department of Electrical Engineering and Computer Science, and Austin Huang, an HST graduate student focused determined the structure of tau protein.

"Tau is 'natively unfolded,' or floppy, so in solution it moves around a lot and can adopt many different structures," Stultz said, much like the individual strands in a bowl of cooked spaghetti. Contrast that to the vast majority of other proteins, whose individual strands have similar structures, like the individual strands of uncooked spaghetti.

"With a 'normal' protein, you can measure the lengths of individual molecules and the average will be a pretty good description of any one," said Stultz.

Tau molecules, however, "are all over the place - they're so diverse that it's difficult to get one measurement that describes all of the possible structures."

Using the new technique called Energy-minima Mapping and Weighting (EMW), they asked a computer to come up with all possible structures of tau that are consistent with an average set of experimental data.

"We generated lots and lots of structures for both normal tau and a mutant form" associated with an increased risk for Alzheimer's, Stultz said.

By comparing the two sets, the researchers found one structure that was more common in the mutant form, and therefore likely to "play a role in the pathologic process." That structure, in turn, could then become the target for a new drug.

The study appears in PLoS Computational Biology.

ANI

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