Alright, sit down. In this article, we’re going to cover prions, precisely, how these viral pathogens cause literal holes in the brain.
We will proceed by first defining prions and prion diseases, then explaining how they are created, to later on list the particularities of these pathogens. Some other points that will be made in the following article include, but are not limited to, diagnosis techniques, as well as examples of prion diseases.
A normal prion protein is a particle most abundant in human and mammal brains that are “likely” to be performing certain functions such as cell signaling or copper binding, however, its functions are not fully understood. Prion diseases, or transmissible spongiform encephalopathies, are fatal neurodegenerative diseases caused by misfolded proteins during the process of post-translational modification of said proteins. Put simply, the normal prion protein interacts with an abnormal protein, resulting in an abnormal prion protein. This “bad” prion then aggregates in the brain and forms fibrils and plaques of amyloid. Amyloid is a waxy, translucent substance consisting primarily of protein that covers certain organs and tissues and leads to diseases such as Alzheimer’s disease. I like to think of it as fatal glue that clumps together to prevent cell function and the passage of neurons. The bad prion can do this because, through its conversion, it acquired a high beta-sheet content. We’re looking at 43% for a bad prion, but only 3% for a normal prion, therefore described as primarily alpha-helical.
Anyway, moving on to some of the terrifying yet fascinating particularities of these prion diseases.
What we know: not much, but we do know this:
- It’s a fatal neurodegenerative disease in men and mammals
- It does not spark any conventional host immune response, making diagnosis very difficult as we can’t measure the level of antibodies in an infected individual.
- It targets the brain and forms “sponge-like” characteristics by essentially eating away at the grey matter.
- Prions are not readily detectable by conventional microscopy.
- Transmission occurs through inoculation and ingestion.
- We can expect to find more than a million infectious units in a single gram of brain tissue -> highly infectious
- The incubation period lasts longer than other infectious diseases, which is decades for humans.
- It is remarkably resistant to conventional decontamination procedures, such as high temperature, ionizing radiation, fixation in formaldehyde, etc.) Side note: formaldehyde reacts to lateral protein chains, forming groups of hydroxy-methyl.
- Therefore, according to Griffiths (1967), prions may be composed entirely of protein? We simply don’t know but it’s a satisfying hypothesis.
As you can see, this sounds like the most monstrous disease one could think of, but it’s also very difficult to detect and treat.
PrP C = good prion, or normal cellular isoform
PrP Sc = bad prion, or disease-associated isoform
It is very difficult to distinguish the two, but the most promising diagnosis technique so far is the “fingerprinting” technique. Because PrP Sc is protease-resistant, enzymes are unable to digest it completely, leaving a “core” which is represented by dark bands, and from which we can distinguish differences in structure, for example.
However, when able to detect the presence of PrP Sc, the diagnosed diseases are heartbreaking, for both humans and animals. The diseases found in animals include scrapie, affecting sheep and goats, chronic wasting disease, affecting deer and elk, BSE (Bovine spongiform encephalopathies), as well as atypical forms of scrapie and BSE. For humans, they include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, Kuru (definitely worth looking into the story behind this one), fatal familial insomnia, and variant Creutzfeldt-Jakob disease (vCJD), as well as a newly discovered prion disease called Protease-sensitive prionopathy (PSPr), for which a case report showed a gentleman presenting the same proteins as those diagnosed with Alzheimer’s disease, Parkinson’s disease, among others.
Professor James Ironside, a neuropathologist, goes into great detail explaining prion diseases and the “detective work” behind the information we have today on these mysterious pathogens. The link to his talk at the University of Edinburgh is pasted down below, and from which the content of this article was primarily gathered. It is undoubtedly worth the 54 minutes.
Sources:
https://www.youtube.com/watch?v=nlIYGYA5q0s: Prof. James Ironside; Prions: The serial killers that attack the brain
Comments