Protein modelling brings hope for dementia treatment

Unraveling the mysteries of proteins whose changed structures cause conditions such as Alzheimer’s and Parkinson’s disease is key to developing new drug treatments for devastating neurological disorders, says a University of Victoria biochemist whose findings are attracting an international audience.

Science has only recently acquired the tools to do the molecular modelling needed to determine a protein’s structure, says Christoph Borchers. His research—featured this month in Science Advances magazine—establishes a mechanism for doing that.

Borchers has developed a method for creating three-dimensional models of cellular proteins. That work, done in collaboration with computational biochemist Nikolay Dokholyan from the University of North Carolina, will shed new light on proteins that change their structure and cause neurological conditions including Alzheimer’s Parkinson’s, and Creutzfeldt-Jakob disease.

Being able to create a model of these tiny structures for the first time clears the way for custom drug treatments for proteins that change their structure in ways that cause disease.

“What happens with a disease like Alzheimer’s is that the protein changes its structure and starts to build a chain that then leads to the plaque in the brain that causes this condition,” says Borchers. “We can interrupt that chain, but we first need to know the ‘key and lock’ that would let us do that. If you know the structure that leads to Alzheimer’s, then you can develop drugs that fit with that structure.”

Until now, scientists could only study a chain of amino acids and make their best guess as to the structure of the protein created by that chain, as proteins are too small to be seen under a microscope. Every gene in human cellular DNA contains the code for a protein structure, the term used for the sequence of amino acids unique to that protein.

“If you know the structure, you can understand the function,” says Borchers. “We’ve always dreamed about this, and now we have shown it’s possible. But now we want to apply it. The next stage is to use this technology to elucidate the structure of disease-involved proteins.”

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