"The process by which this change occurs is not clear and there is a great deal of work under way to establish the structure of the prion protein in both its normal and aberrant forms. Recently scientists have developed a molecular model of both variants and have published papers describing the structure of prion proteins (as manufactured by E. coli bacteria that were altered through recombinant DNA techniques). Further work using magnetic resonance imaging and x-ray crystallography should help us understand the key structural elements that allow the prion to co-opt the normal cellular form into the disease-producing variant. It is likely that other cellular components assist in this process, so work on understanding the cell biology of both forms of the protein is also vital."

Shaun Heaphy in the department of microbiology and immunology at Leicester University provides this overview:

"A number of fatal neurodegenerative diseases in humans--such as Creutzfeldt-Jakob disease (CJD), kuru and Gerstmann-Str¿ussler-Scheinker (GSS) disease--are thought to be caused by an infectious agent known as a prion. Prions also cause disease in a wide variety of other animals, including scrapie in sheep and bovine spongiform encephalopathy (BSE) in cows. Collectively these diseases are known as transmissible spongiform encephalopathies.

"The cause of CJD was unknown for many years; it occurred seemingly randomly, at a very low incidence. In the 1950s an epidemic transmissible disease called kuru, similar to CJD, was identified in the Fore tribe of Papua New Guinea. Transmission of the disease occurred during a ritual funeral process in which the brain of a dead tribe member was removed from the skull, cooked and eaten. Scientific analysis of the brains of people who had died from CJD or kuru showed that their brain tissue had a spongiform appearance, that is, there were holes where cells ought to be, indicating an encephalopathy, or reduction in the number of brain cells.

D. Carleton Gajdusek, working at the U.S. National Institutes of Health, demonstrated that extracts of brain prepared from people who had died of CJD or kuru could cause a similar disease when inoculated into the brain of chimpanzees. These experiments obviously suggested the presence of an infectious agent. That inference has been confirmed by the inadvertent transmission of CJD to patients undergoing various medical treatments, such as corneal transplants and human growth hormone therapy.

"Confusingly, researchers also recognized that some prion diseases, such as GSS, were inherited. The pattern of inheritance was recognized as being autosomal and dominant, meaning that if a parent developed GSS, there was a 50 percent chance that a child of either sex would also develop the disease. Any explanation for the cause of a prion disease therefore has to account for random, inherited and transmitted variants of the disease.

"Although there is not yet a universally accepted explanation of this puzzle, progress is being made. We now know that a normal cellular protein, called PrP ( for proteinaceous infectious particle) and which is found in all of us, is centrally involved in the spread of prion diseases. This protein consists of about 250 amino acids.

"Some researchers believe that the prions are formed when PrP associates with a foreign pathogenic nucleic acid. This is called the virino hypothesis. (Viruses consist of proteins and nucleic acids that are specified by the virus genome. A virino would also consist of proteins and nucleic acids, but the protein component is specified by the host genome, not the pathogen genome). In support of the virino hypothesis is the existence of different strains of prions that cause differing patterns of disease and breed true; the existence of strains in pathogens is usually the result of changes in the nucleic acid sequence of the infectious agent. Scientists have not found any nucleic acid associated with a prion, however, despite intensive efforts in many laboratories. Furthermore, prions appear to remain infectious even after being exposed to treatments that destroy nucleic acids.

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