The Mysterious Infectious Agents: Prions

Most of us basically know what pathogens are, the species that causes sickness, which are the creatures that have a nucleic acid genome such as bacteria or viruses have. The common feature between those species is that they all have DNA or RNA. So, what if there are some molecules which we cannot call them alive or are not actually creatures which has nucleic acid genome and also give you deadly diseases? In 1997, American biologist Stanley B. Prusiner, who has won a Nobel Prize from his discovery, discovered a mysterious agent which is called “prion” that has the ability to make one sick, but has no nucleic acid.

Deadly Misfolded Proteins

Proteins are the molecules which determine the unique functions of our cells. Every protein has its own three-dimensional (3D) structure and the process by which a polypeptide folds into its final 3D structure is very complex and intricate. So what happens when a polypeptide begins folding with the correct primary structure and ends up being folded incorrectly? Because of every protein has has its own special function determined by its own 3D structure and amino acid sequence, in case it folds incorrectly, the function won’t be the same.

Normally, since the misfolded proteins in our cells are biologically inactive and non functional, our body either denatures and breaks down those proteins or refolds them into the correct structure. In rare cases, these misfolded proteins can actually form the biological molecules which we call “prions”.

Prions are dangerous infectious agents that cause various types of deadly diseases not only in humans, but also in animals. For instance; Mad Cow Disease, Creutzfeldt-Jakob Disease, Fatal Familial Insomnia, Bovine Spongiform Encephalopathy are some of the most known diseases caused by prions.

What Exactly a Prion and What are Their Properties?

Prions are aggregate molecules, collection of proteins, that normally exist in our body but which have misfolded. Because of this misfolding, they form insoluble aggregates which means there is no way our body can break them down and denature them by the same method as it normally does. Those aggregate proteins will somehow cause the death of the cells and eventually that individual.

A: PrPC (correctly folded protein)

B: PrPSC (misfolded protein)

The following molecule PrPC normally exist in our brain cells, our neurons. Under certain conditions like if some mutation occurs, PrPC misfolds into the infected molecule PrPSC. One of the major differences between those two molecules is that PrPC consists predominantly of alpha helix structure meanwhile PrPSC consists predominantly of beta pleated sheets. Therefore, because of the structure of beta pleated sheets (linear polymers of amino acids), PrPSC has a high propensity of bonding to other molecules which also contain beta pleated sheets.

In case a normal protein which is normally found in our brain cells transforms into PrPSC, because of the high potential of bonding oof beta pleated sheets via noncovalent bonds, it can basically form aggregates with other proteins and that will form even larger infected molecules which we call amyloid fibers.

What is the Big Deal With Amyloid Fibers?

Since those amyloid fibers cannot be broken down by our cells and get even larger, eventually this situation ends up with deaths of many neurons in our brain. If we examine the brain of an individual who has a prion disease, we will see a sponge-like brain structure (spongiform), a brain which contains many holes and those holes are results of the fact that many nerve cells have died. Recently, we considered only bacterial cells and viruses as the species that are capable of infecting our bodies, but now we know those aggregates can also act like infectious agents.