Prions 1982 – Diseases Caused by Abnormal Proteins

Just as the fictional story of Dr. Jekyll and Mr. Hyde places both a good and an evil personality within the same person, devastating prion diseases appear to be caused by a protein with two forms, one useful and one destructive. 

In 1982, the American neurologist and biochemist Stanley Prusiner coined the term prion when he identified a disease-causing agent that appeared to consist only of protein. By contrast, even viruses contain genetic information in the form of DNA or RNA as well as protein.

The small prion protein (PrP) has at least two different three-dimensional shapes.

• In its normal cellular form (PrP-C), this protein may serve several useful purposes, such as maintaining the insulation that facilitates the transmission of electrical signals along nerve fibers. 
• In its lethal form (PrP-Sc, where Sc refers to scrapie, a prion disease of sheep), this protein causes destruction in the brain. 

Some prion diseases, such as Creutzfeldt-Jakob disease, can be passed genetically to the next generation through a mutation in the gene encoding PrP. However, the same type of disease can also be acquired by eating beef infected with prions. In cattle, the disease is known as bovine spongiform encephalopathy (BSE) or “mad cow” disease. 

Another example of an acquired prion disease, studied by the American physician Daniel Gajdusek among the Fore people of Papua New Guinea, is kuru. Kuru appears to result from eating the infected brains of deceased relatives.

Researchers are still investigating how lethal PrP-Sc converts normal PrP-C into more PrP-Sc. The abnormal protein accumulates in the brain, forms clusters and destroys brain cells, creating spongelike holes and causing loss of motor control, dementia and death. Unfortunately, PrP-Sc is highly stable and resists destruction by chemical and physical agents. It also does not trigger inflammation, and the immune system does not mobilize to fight the disease. Genetically engineered mice that do not produce PrP cannot develop prion disease.

Historical Figures Mentioned in the Article: Stanley Ben Prusiner (b. 1942), Daniel Carleton Gajdusek (1923– 2008)

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