Sunday, December 9, 2018

The Bright Side of the Prions

        Prions, the proteins responsible for diseases like Creutzfeldt-Jakob (CJD) disease, have been becoming more and more ubiquitous in transplant recipients over the past couple of years. Prions, which are sometime referred to as proteinacious infectious particles, are misfolded protein molecules that can spread by causing other proteins to fold upon coming into contact. Scientist have studied these infectious protein molecule for sometime now, however, it was Carleton Gajdusek who originally discovered that, unlike other proteins, Prions lack the nucleic acid building blocks that are normally present in normal protein molecules. A little refresher about the structure and formations of proteins might be beneficial before continuing. As most of us already know, proteins consist of hundreds of amino acids that form long polymers chains. These long polymer chains give rise to an enormous amount of structural and functional variety. Despite their diversity, all protein molecules start with the basic amino acid sub-unit building blocks that makeup a polypeptide chain. The primary structure of a polypeptide chain undergoes a series of folding processes that eventually results in either secondary (α helix and the β pleated sheets), tertiary or quarternary structures. These long polymer chains fold into three dimensional polypeptide chains through hydrogen bonding, however, sometimes protein chains misfold during this process. Misfloded proteins are usually deactivated when this happens but when they remain active they can mutate and form Prions. According to an article posted on the NCBI website, Prions can survive in heat up to 200 °C for a couple of hours and adhere to stainless steel within minutes and remain infectious for long periods of time. The fact that Prions can survive such thorough decontamination processes means that they're easy to pass onto others. In addition to this, Prions are toxic and can cause neurodegenerative diseases but whats worse is that they're extremely resistant to disinfectants and sterilization methods. 
      This brings us to a recent concern surrounding the spread of Prions through infected organ donors. According to an article in Scientific American there is a growing epidemic of infected donors that are passing down infectious proteins. Apparently, the proteinacious infected particles have been identified in the corneas of donors who transmitted the disease on a number of occasions. According to a study posted in the scientific journal mBIO, researchers found that prion infected individual's corneas were riddled with infectious particles way before they ever exhibited symptoms. The presence of these prions found on the surface of the eye were caused by the weakening of the cornea, which allowed the infectious particles to exit through tiny neural conduits. This fortuitous observation has given doctors a way to screen for the hard to diagnose infection through methods such as electroretinograms. Because cornea transplants are becoming increasingly popular ( According to Scientific American 64,000 cornea transplants are performed each year in the US) this breakthrough arrived at a critical time and can be instrumental in developing preventative measures that stop this growing epidemic.   


  1. I have a couple questions regarding the production of prions themselves. First of all, I am curious on how the polypeptide chains misfold. Also when they do misfold, why is it sometimes that they deactivate and sometimes they do not. In other words what is triggering the deactivation of the protein.
    My other question is that are the prions only produced near the cornea or do they travel there from throughout the body? If they are produced in that general area, why is that. I understand that from the article it is known that they can escape through the cornea by weakening it but can it not travel through bodily fluids?

  2. Those are all good questions Anthony. Polypeptide chains fold for a number of reasons among some of these reasons are hydrogen bonding, van der Waals forces and electrostatic interactions. The angle at which these proteins denature are due to sterics as well. I believe the most important aspect of why protein molecules fold in the first place is due to the fact that certain conformations are lower in energy than others. Basically the inter and intra-molecular forces repel and attract at different areas in order to achieve entropy. I believe there are software programs dedicated to understanding and subsequently predicting folding patterns of large polypeptide chains. As far as deactivation goes, I believe it can be sterilized through some sort of metabolic process. I know NO2 can effectively deactivate at low concentrations and room temp. but besides that I'm not sure of any other methods.
    Prions are not localized in one specific area, in fact they can also be found in the central nervous system. They can be found in the brain and the spinal cord. As far as the brain goes I'm not entirely sure where they're at but I know they can be found in the meninges tissue surrounding the spinal cord. To answer your next question, Prions can travel throughout your body in three ways; cell-to-cell contact, tunnelling nanotubes and through exosomes.

  3. I hope that answered your question, at least in part.

  4. I am new to genetics and knew very little about Prions which is what sparked my interest in reading this post. Very informative. Thank you for the brief back ground on healthy protein structures. As I was reading I kept thinking, we need to discover a method to screen for Prions. I was please to read towards the end that indeed we have with the invention of electroretinograms.