Altered prion protein leads to an infectious prion disease

A group of researchers at the University of Zurich around Professor Adriano Aguzzi (Institute of Neuropathology) has found that subtle changes in the structure of the prion protein lead to a serious neurological dysfunction. In addition, they showed that the mutated protein leads to an infectious disease. Her research results have been since 1. December 2008 published online on "Proceedings of the National Academy of Sciences" (PNAS).

The aim of the study was to elucidate the development of "Chronic Wasting Disease" (CWD) in deer and elk, a highly infectious prion disease similar to bovine spongiform encephalopathy in cattle (BSE, or mad cow disease) and Creutzfeldt-Jakob disease in humans. It affects up to 20 percent of all deer in the United States. It is believed that prion diseases result from incorrect folding of the prion protein. The misfolding creates plaques in the brain, which are then likely to "infect" other proteins.

The researchers introduced two point mutations in the mouse prion gene so that the mutated protein resembled the elk prion gene. These changes resulted in a stiffening of the protein structure. Surprisingly, mice that produced the stiffened prion protein developed plaques in the brain and neurological symptoms such as prion disease.

"We were really amazed to find that inoculation with brain extracts from our transgenic mice caused disease in normal mice. That means that the mutated protein is sufficient to cause an infectious disease," said Aguzzi.

These research results show that just two point mutations in the prion gene are sufficient to set off a contagious prion disease. Prof. Aguzzi said: "These results confirm the hypothesis that prions consist exclusively of proteins and suggest that the prion diseases of elk and deer have a genetic component."

Source: Zurich [UZ]