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Staying ahead of Huntington's disease
Date:12/11/2013

ant in this regard because they enable us to learn from nature's own strategies.

"Previous studies from other labs showed that the toxic effects of polyglutamine expansions are tempered by the sequence contexts of polyglutamine tracts in Htt, not just the lengths of the polyglutamine tracts", Pappu says.

He and his research team focused on understanding the effects of sequence stretches that lie on either side of the polyglutamine tract in Htt. The results show that the N-terminal stretch accelerates the formation of ordered structures that are presumed to be benign to cells, whereas the C-terminal stretch slows the overall transition into structures that are expected to create trouble for cells, suggesting that these naturally occurring sequences behave as gatekeepers.

"It appears that where polyglutamine stretches are of functional importance, nature has ensured that they are flanked by gatekeeping sequences," Pappu says.

Pappu and his team are now working to find way s to mimic the effects of the N- and C-terminal flanking sequences from Htt. His team is working closely with Marc Diamond, MD, the David Clayson Professor of Neurology at the School of Medicine, to understand how naturally occurring proteins interact with flanking sequences and see if they can coopt them to ameliorate the toxic functions in the polyglutamine expansions.


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Contact: Neil Schoenherr
nschoenherr@wustl.edu
314-935-5235
Washington University in St. Louis
Source:Eurekalert  

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