There is no consensus nor concision when it comes to defining a prion. While one may attempt to rudimentarily introduce a prion as an infectious protein agent, even this may be contested—Prions do not always necessary cause disease nor are they proteins in a classical sense, with some definitions describing them as “proteinaceous”. The most common way in which someone may be acquainted with prions and their nature is through their knowledge of Bovine Spongiform Encephalopathy, ‘Mad Cow Disease’ (BSE). While the true modem operandi of the prions causing this disease are still not understood, the fact that they were transmissible and could affect humans, via consumption of beef, resonated with the public. There are websites and abundant information assuring the public of the safety of the beef industry within the United States, explaining away the fear associated with the mystery of the disease, though most of this information is not purely scientific and unbiased, as it is funded by entities such as the National Cattlemen’s Beef Association2. What does the scientific community have to say about prions?
The biggest question that scientists are still pursuing, concerning prions, is their origin. They seek insight by better understanding their nature: it is known that they are the smallest known infectious particle, contain no genetic information (and therefore are not classified as viral, bacterial, nor fungal), that they are practically the exact same as the original protein they originated from (save for a few abnormal folds in their structure), and that they cause disease by inducing normally folded proteins to mis-form (rather than multiplying themselves)1,3. The most widely understood prion is PrPSc (Sc=Scrapie, a spongiform encephalopathy in sheep and the first discovered prion disease), which is a general term referring to any infectious form of the normal PrPc (c=cellular) prion protein but generally refers to BSE. This nomenclature is confusing and possibly misleading in that it may seem as if PrPc is a unique protein in that it has different content or function, though it does not—it simply is distinguishable through its nucleotide sequence, and therefore folding, and has been identified and predominantly exists in the nervous system, though it is found in other areas of the body in small amounts5.
PrPSc is mainly distinct in its resistance to proteases, which break down proteins, such that they are not destroyed in accordance with endocrine signaling or a pre-programmed lifespan such as healthy proteins are. While the folding in the infectious form of the protein is different, containing more B-sheets than a-helixes, causing greater differences in the ultimate shape of the protein by altering smaller pieces that are meant to fit together (B-sheets are denser and more flattened longitudinally than a-helixes), the resistance to degradation is attributed mainly to the formation of amyloid plaques. When the protein structure is altered by the greater B-sheet content, a certain ‘pocket’ is created in the protein such that the PrPSc proteins naturally tend to form linear aggregations because there is an out-pocketing on the anterior end of ever prion that fits into an in-pocketing on the posterior end of another prion; they stack together like Lego’s. This is due, on a chemical level, to hydrogen bonding between glutamine’s nitrogens and carbons in the two interacting, antiparallel B-sheets6. The disease symptoms of neurological degeneration, in an exponential fashion, which inevitably ends in death (no cures or treatments exist) are less obvious in cattle, but distinct and crippling in the same disease within humans, called Creutzfeldt-Jakob disease. Other implications can be seizures and impaired immunological response.
Spongiform encephalopathies, including both the bovine and Creutzfeldt-Jakob diseases, are so called for the visible effects of the amyloid plaque formation: brain tissue from a diseased individual, under a light microscope, appears “spongy”, and vacuolated due to many holes left from penetration by amyloid plaques, composed of PrPSc2. It is clear then, that it is not the actual mis-folding of the prion protein or the effects that this directly employs, as may be assumed, but the plaque formation and its damage to other healthy tissues and structures via amyloid plaques that causes the deadly symptoms of spongiform encephalopathies.
It is established that prions are not strictly proteins, due to their infectious ability to induce other proteins to fold in strange ways, making them virus-like (though this process is not understood) yet how is it then possible that such a prion could exist and not be infectious? This is simply a fundamental flaw in prion nomenclature: the healthy, precursor protein which becomes PrPSc is also named a prion protein, PrPc, though it is not a prion in any classical feature of a prion protein which defines it. If it were not for this confusing nomenclature, prion proteins would indeed all be infectious, yet they are not due to this convention. Some may also argue that even PrPSc is not infectious since the actual protein and its function/lack thereof does not manifest into symptoms, but rather the structures that it forms does. In addition, as a further complication, prions have recently been discovered in lower organisms—some plants and yeast, saccharomyces cerevisiae—that don’t have any obvious effects.
There is a vast amount of information yet to be grasped regarding the scope and origin of prions, yet for the prions that directly affect our lives, there is a solid definition such that a general understanding of them can be secured. It is also known, with certainty, that the same mechanism and prion proteins cause Gerstmann-Straussier-Scheinker syndrome (which is familial, i.e. inherited) and Kuru (caused by cannibalism) in humans as well as Scrapie (in sheep), Chronic Wasting Disease (in hoofed, horned animals), and various other animal-specific spongiform encephalopathies in other organisms, with all of these diseases possessing similar symptoms to Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease.
Moving forward, in order to be able to more concisely and accurately define prions, their nature must first be better understood. In addition to this, though, it would be beneficial for the public to be exposed to more unbiased yet informed information on prions, which perhaps is appropriate currently, now that fear surrounding the mad-cow ‘epidemic’ has subsided. There is also amyloid plaque formation in dementia, causing the same degenerative neurological symptoms (though their formation is attributed to other factors than prions), so this may be a good opportunity for education on prion diseases whether it be through an article, news report, or explanation by a personal doctor. Ultimately prions, as we know them (and disregarding misleading nomenclature), are spontaneously arising mis-folded proteins, mainly in the nervous system and brain, which can induce other healthy proteins to become misfolded simply by being near them and act as infectious agents, since these misfolded proteins aggregate into plaques which damage the brain and inevitably end to death after mounting neurological manifestations; while the prion proteins spontaneously arise, once they exist they can be transmitted via ingestion of infected tissue.
A study in Canada on the public’s perception of prion diseases claimed that
Overall, respondents felt well informed about the risk issue. The majority (72%) of respondents were aware that “it was likely that cows could get mad cow disease if they ate contaminated feed prepared using cow carcasses.” However, the awareness level of participants was lower regarding other risk issues. When asked if they thought “it was likely that an animal could be infected with mad cow disease without showing symptoms” half of respondents (51%) stated that they very much or extremely believed this to be the case. Moreover, 55% of respondents thought “it was likely that humans would become infected with the human form of mad cow disease if they ate contaminated beef.” Lastly, 43% believed very much or extremely that “it is likely that wild game could develop diseases similar to mad cow disease.”
While all of this, concerning “Mad Cow Disease,” is impressive and it is calming to know that the public know some facts about the true nature of the disease despite fear-fueled claims on the internet, the fact that “29% believed there was no or little uncertainty about BSE risks,” supports the claims of this whole report: the public is not aware of the uncertainty surrounding the mechanism of infection via prions. So, despite the large awareness of facts about the disease which people might perceive to be personally consequential, there is no speculation into the why or how of these facts and is indicative of the overall public’s lack of scientific inquisition and tendency to blindly accept “facts” presented to them.
Ferrier, Denise R., and Richard A. Harvey. Lippincott’s illustrated reviews: biochemistry. 5th ed.