Misfolded proteins and mad cows
Proteins are essential components of the human body. So what happens when certain proteins fold into the wrong shapes and become infectious agents?
Story by Laura Ly
In 1982 a scientist by the name of Dr. Stanley Prusiner published a paper suggesting that certain proteins in the brain, which he called "prions", caused certain neurodegenerative diseases. His claim ignited a firestorm of controversy in the scientific community. Scientists believed that a virus could cause degenerative brain diseases; but they were hostile to the idea that a protein could become infectious and do the same. Dr. Prusiner persevered, however, and in 1997 his work was recognized with the Nobel Prize for Medicine. Today, more than a quarter of a century after the original publication, the devastating effects of prion diseases are universally acknowledged.
AHFMR Scientist Dr. David Westaway was involved with that prion research almost from the start. From 1985 onward he worked with Dr. Prusiner on the first experiments to establish the molecular biology of the prion. Now he investigates how prions cause such brain disorders as Creutzfeldt-Jakob disease, chronic wasting disease, and bovine spongiform encephalopathy -also known as BSE or "mad cow disease"-an infection especially relevant to Alberta's beef industry.
Proteins play a role in the structure, function, and regulation of the body's cells, tissues, and organs. "Protein molecules are like the verbs in a sentence-they carry out the actions," explains Dr. Westaway. All protein molecules fold into three-dimensional shapes; but when they change into the wrong shapes (a process known as misfolding), they can cause brain diseases. Prions are a special type of brain protein that are normally harmless, but once they fold abnormally, they become infectious from host to host, and across species. The diseased proteins then clump together, slowly infecting and destroying the brain.
Dr. Westaway and his team recently discovered another brain protein in the same family. The Shadoo protein is a "cousin" of the normal protein, and is found in significant quantities in the adult brain. However, Dr. Westaway observed that as the prion infection increases and the host gets sick, the Shadoo protein begins to disappear. "We now know that the disappearance of the Shadoo protein has to do exclusively with the accumulation of the infectious form. It was an unexpected finding, and it's something we are eager to understand in greater depth."
Alzheimer's disease, a non-infectious protein folding disease of a type that also includes Parkinson's, is another area of research for Dr. Westaway. He and his team focus their attention on the accumulation of a particular peptide (a miniprotein) believed to cause the disease. Through study of the peptide, Dr. Westaway hopes to understand the chain of chemical events that causes Alzheimer's and, in the wake of that understanding, develop potential treatments.
A molecular biologist by training, Dr. Westaway was recruited to Edmonton from the University of Toronto in 2006. "The resources within Alberta were a perfect match for us to pursue prion research on an international level," he says. "There was a good, open-minded collegial atmosphere on the university campus that made it an attractive prospect."
Dr. Westaway is the director of the newly established Centre for Prions and Protein Folding Diseases at the University of Alberta. Here he hopes to develop different types of preventive strategies for prion folding diseases; in particular, mad cow disease. He notes, "Our primary goal is to understand how a normal brain protein ends up in the wrong shape, what we can do to prevent that, to diagnose that, and to understand how that can happen spontaneously in brain cells."