Creutzfeldt-Jakob Disease

The demonstration of transmissibility produced a search for the infectious agent. Initially researchers believed that a virus must be involved, but by the early 1980s the prion hypothesis had been proposed. "Prion" is a term coined by Dr. Stanley Prusiner in 1982 to indicate that the agent is both a protein and infectious. Prusiner, a University of California neurologist, received the 1997 Nobel Prize in medicine for his work on this new class of infectious agent.

The prion protein is a normal constituent of the human body, and although the exact function is unknown, it is involved in neuron development and prevention of neuronal cell death. The abnormal form of the protein has an insoluble conformation; that is, the protein folds in such a way that it can not easily interact with other body molecules. Since the abnormal form is resistant to degradation by normal body enzymes, it is termed protease-resistant prion protein. The abnormal protein can both accumulate into plaques and induce normal prion protein, in a chain reaction, to transform into the abnormal conformation. The prion protein is concentrated in nervous tissue but can also be found in other tissues, particularly white blood cells and the lymphatic system.

The prion hypothesis explains many of the characteristics of the Transmissible Spongiform Encephalopathies: how a familial disease could be infectious (the inheritance is due to a mutation in the prion gene, but the resultant abnormal protein can induce the conformational chain reaction in people without the mutation); why the agent is so resistant to disinfection (most viruses or bacteria are more susceptible to heat or detergents than insoluble proteins are); and how a disease can be infectious without the involvement of any DNA. The best evidence for the prion hypothesis comes from work on self-propagating prions of yeast.