Posted on 28 March 2017
Previous work from these research teams investigated a class of diseases called tauopathies, which occur when tau proteins spontaneously group together in the brain. It is often associated with Alzheimer’s and other neurodegenerative diseases.
Research has shown that the tau protein can be modified by a sugar, natural to the body, called O-GlcNAc. This sugar can stabilise the protein to block it from clumping together and may thereby prevent disease. The human enzyme O-GlcNAc-hydrolase, however, is responsible for the removal of this crucial sugar from the protein, making it a prime target in preventing the progression of tau-related dementias.
In order to understand how this clumping of tau could be prevented or reduced by increasing O-GlcNAc, scientists at York investigated the structure of the human enzyme to reveal how it is organised to function in this way.
Professor Gideon Davies said: “Inhibiting the O-GlcNAc-hydrolase enzyme allows scientists to stabilise tau. We have solved the three-dimensional structure of the enzyme in order to aid structure-based drug design. The unusual and complex organisation should help us in the search for new drugs to treat neurodegenerative diseases.
“Drugs can be designed based on the 3D structure of this human enzyme, which will ultimately pave the way for new breakthroughs in the treatment of diseases such as Alzheimer’s.”
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The research, published in Nature Chemical Biology, is supported by the Biotechnology and Biological Research Council (BBSRC), Brain Canada, the Canadian Institutes of Health Research, and Alzheimer’s Research UK.