About Prions


Prion disease isn’t common, affecting only about one in a million people each year.  Yet, currently incurable and capable of 100% lethality, there is good reason why they are feared.  Virtually indestructible, the prions that cause prion disease are resistant to heat, radiation, and other techniques that are commonly used for sterilization.


Why so serious?


The first observation of prion disease was scrapie, a disease affecting sheep, discovered by herdsmen in England, France, and Germany in the 1700’s.  The affected sheep would rub themselves against trees or buildings, hence the name “scrapie.”  But at that time, nothing was known about the cause of scrapie or the method of transmission.

The event that brought attention to prion disease was an epidemic of mad cow disease (Bovine spongiform encephalopathy) in the United Kingdom in the 1980’s.  The outbreak resulted in the infection of over 180,000 cattle, prompting the forced slaughter of over 4 million cattle.  In addition, over 160 cases of vCJD (variant Cruetzfeldt-Jakob Disease), the speculated human form of prion disease arising from mad cow disease, had been reported as well.

So what exactly are these prions that cause prion disease?  First, we must go through a brief overview of protein structure.

Proteins and Prion structure

Proteins are large organic macromolecules made up of building blocks called amino acids.  There are about 20 natural amino acids, and the order in which they are linked to form a protein gives the protein specific properties.  However, protein properties are not only determined by the order that these amino acids are linked, but are determined based on four levels of structure.  These four levels of structure are:

  1. Primary structure

  2. This describes the sequence of amino acids that are linked together to form

  3. Secondary Structure 

  4. The chemical composition of the amino acids, containing hydrogen and oxygen atoms, allows one amino acid to hydrogen bond to another amino acid, resulting in the formation of an alpha helix of the sequence of amino acid, or a beta pleated sheet of the amino acids, depending on the nature of the hydrogen bonds. 

  5. Tertiary structure

  6. More interactions within this chain of amino acids, including hydrogen bonding and hydrophobic interactions, results in the folding of the sequence of amino acids into an overall three dimensional arrangement.

  7. Quaternary structure

  8. Many of these tertiary structures can come together to form a fully functioning protein.

The overall nature of a protein is determined by all levels of structure.  For example, even one single exchange of amino acids in the primary structure may lead to different bonding and interactions, leading to a changes in the secondary structure, and misfolding of the tertiary and quaternary structure, and leading to the inactivity of the protein. 

Proteins do occasionally misfold.  Below is a diagram of a protein that interacts with another protein, causing it to misfold. 

Normally, misfolded proteins are degraded in organisms by an internal check mechanism.  However, some misfolded proteins are resistant to this natural degradation process.  There are many diseases associated with misfolded proteins, including Alzheimers and Parkinsons disease.

Prions are also misfolded proteins.  However, prions have the frightening ability to convert normal proteins into more prion proteins, making them infectious and capable of multiplying.  In mammals, the normal protein called PrPc (c for cellular) can be misfolded into the self-propagating prion form, called PrPsc (sc for scrapie, the first prion disease observed).  The two forms of the protein, PrPc and PrPsc have the same primary structure.  In other words, the sequence of amino acids that make up the protein are identical for both forms.  However, PrPsc has been misfolded, and is capable of converting more normal proteins into the PrPsc form of the protein.

To learn more about the way these prion proteins are transmitted, click the arrow below.