New discovery may lead to improved drugs for Alzheimer's
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
