WHAT IS A PRION? Stanley Prusiner and the Prion

There are many diseases which don't make sense to scientists. Some of these have been around for years, yet there is no bacteria or virus known to cause them. One such disease is Creutzfeldt-Jakob Disease, otherwise known as CJD. The main symptom is swiftly progressing dementia which usually occurs later in life. This disease can arise spontaneously, or sporadically appear in family lines.^{(Prusiner Prion 49)} In all cases, the disease is fatal.

A woman with CJD went to see Doctor Stanley Prusiner at the University of California, San Fransisco School of Medicine. Like all such patients showing symptoms, her loss of ability was evident and she quickly progressed toward death. She wasn't any different from other CJD sufferers. Her case was fatal, but something else happened as a result of her death: Prusiner's interests were piqued. He vowed to find the cause of CJD and started researching. He did a great deal of reading, then years of experimenting. Through detailed research, he concluded that there wasn't a bacteria or virus at work, but a protein which he later called a prion.^{(Prion 49-50)}

Prions Defined

So, what are these curious particles? Essentially, they are nothing more than a bent protein. The name "prion" is really shorthand for the words "proteinaceous infectious particles."^{(Prusiner Prion 48)} These proteins have a specific amino acid composition, although their shape can differ. It is these differences in shape that lead to the problem.

All mammals have prions as a normal part of brain composition. For the most part, the prion protein is harmless and natural. Scientists have given it the name PrP^C, which stands for prion protein, cellular. In a very few cases, the protein bends into a different shape. When this transformation takes place, the protein cannot be broken down by the normal biological pathways.^{(Cohen et al 531)} It becomes a permanent fixture of the brain. These particles are known as PrP^Sc, designating a scrapie, or bent protein.

If PrP^Sc simply failed to decompose, there might not be a significant problem. Unfortunately, these prions have another effect: they can replicate themselves. Because of this, Prusiner originally thought they were alive.^{(Ponte 128)} Generally, few scientists hold this notion, and even Prusiner now refers to these particles as simply a class of pathogens.^{(Home Page 1)} Although not another form of life, prions are remarkable in their structures and functions.

The Protein Structure of Prions

Protein usually comes in two forms. The first is a loosely bound helical shape, somewhat resembling a strand of DNA. This spring-shaped chain can be easily built and also easily destroyed. The body prefers to use these helices, called helices, because they can be manipulated by enzymes and chemicals. The second form is much more rigid and stable.^{(Cohen et al 531)} Instead of the helix, it forms a pleated sheet, called a sheet, which isn't easily destroyed by the body. Prions come in these two forms. The normal protein, PrP^C, is composed largely of helices so that the body can create and destroy them without difficulty. The rogue protein, or disease causing prion, forms sheets instead.^{(Prusiner Prion and BSE 245)}

The normal protein shows the prevalence of helices, in green, and the rogue protein (PrPSc) shows increase in pleating, in blue.

The theory which intrigues the scientific world so much is that a normal prion can convert to a rogue protein, causing distortion in the tissues.^{(Prusiner Biology 656)} This may happen at a single amino acid site. These distortions produce the symptoms of diseases like CJD and the animal disease known as scrapie.

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