Prions: Proteins with Attitude
Prions are the smallest pathogens known to man. These protein particles do not possess genetic material and have extremely simple structures. What they lack in complexity, they make up for in dangerousness. A sickness caused by a prion leads to the decomposition of the brain tissue and inevitably to death. Prions are not only the smallest but also the most recently discovered pathogens. Much about their operation and about the options for treatment still requires detailed research.
Prion-related sicknesses have been observed for a long time, but it was in the 1980s when scientists first became aware of this pathogen. Stanley Prusiner published his “prion hypothesis” in 1982.” His hypothesis suggested that tiny protinaceous particles without genetic material are responsible for diseases such as Creutzfeldt-Jakob disease. Prusiner's theory was controversial as it was believed that infections can only be caused by living pathogens such as viruses or bacteria. With the peak of the mad cow disease crisis fifteen years later, it was finally proven that these tiny particles are indeed able to force healthy proteins to transform into duplicate pathogenic prions. As a late scientific triumph, Prusiner won the Nobel Prize in Medicine in 1997.
A Lethal Pleating
Prions are tiny particles between 4 and 6 nanometers (nm) in length. Compare this to the second-smallest pathogen, viruses, which are between 15 and 400 nanometers. Prions have no nucleic acids—neither DNA nor RNA.
The name prion was derived from the phrase “proteinaceous infectious particle.” Yet this name does not do justice to the prion. Prions are also able to exist as natural cellular proteins (PrPc) in human and animals without causing symptoms or problems. Normally they attach to the nerve cells called neurons. In the case of an infection, the PrPc changes its structure, while the components remain the same. The beta-pleated sheet responsible for the organization of amino acids in proteins redesigns the cell architecture. Thus emerges the PrPsc, a pathogenic protein with entirely new and dangerous characteristics.
A prion is not able to reproduce. It can, however, cause other proteins to abandon their current structure and transform into prions. An uncontrollable chain reaction is thereby developed, like a giant snowball effect, as more and more proteins transform from PrPc into PrPsc and the danger escalates.
Starting with the Neurons
Benign PrPc particles are located in the neurons of the spinal cord and brain, and it is from there that a prion infection begins. A prion infection ensures that a rapid progression of the symptoms accompanies the brutally fast decay of the body. The body has simply no way to reduce or destroy the prions. They enter cells that eventually die from their presence. The brain almost becomes spongy and develops actual holes. The disease is highly lethal.
Diseases Caused by Prions
| Humans | Animals |
|---|---|
| Creutzfeldt-Jakob Disease (CJD) | Scrapie in sheep and goats |
| Variant Creutzfeld-Jakob Disease (vCJD) | Bovine Spongiform Encephalopathy (BSE), also known as mad cow disease |
| Kuru (epidemic in Papua New Guinea) | |
| Gerstmann-Sträussler-Scheinker Syndrome (GSS) | |
| Fatal familial insomnia (FFI) |
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The Domino Effect
Today's scientists have identified three ways in which prion infections can occur:
- Sporadic Prion Infection. A PrPc can spontaneously mutate into a PrPsc. This “unfolded” prion unfolds other prions and thereby starts the lethal domino effect.
- Genetically Triggered Prion Infection. It is possible that a gene responsible for amino acids is mutated. One possible result of this mutation is that some proteins end up in the form of a PrPsc. Fatal familial insomnia (FFI) is a genetically triggered prion infection. Every individual with this rare disease has inherited it from a parent who was a carrier.
- Transmittable Prion Infection. In most cases, the transmission takes place through food intake. This can occur by consuming BSE-contaminated beef (variant Creutzfeld-Jakob Disease (vCJD)). Animals can also acquire this disease if they are fed meat-and-bone meal, which has meanwhile been outlawed. Other proven paths of infection include blood transfusions and the use of contaminated neurosurgery OP instruments. Airborne and smear infections are also theoretically possible but have not been proven.
Cloaked and Armored
The transformed prions are still very similar to the PrPc as they contain the same components. This camouflage works: the body is unable to identify the PrPsc particles as enemies and develop any defensive measures. The disease is first identified when the symptoms are fully developed. An etiological treatment is currently not available. It is now only possible to medically treat the symptoms.
Outside the human body, prions have shown themselves to be surprisingly resistant. They are able to survive for years on materials and on the ground. High temperatures, UV radiation, radioactivity, and chemicals seem to have no effect on these resilient proteins. Common medical disinfectants are not strong enough to stop the risk of infection. A prion can only be destroyed in a high-pressure autoclave through a one-hour exposure time at 200ºC.
A prion infection in a dentist's office has never been substantiated. This does not mean, however, that prions will not play a significant role in the future.
