Prions are unique infectious agents that differ fundamentally from conventional pathogens like bacteria, viruses, or fungi. They are not living organisms but rather misfolded proteins that cause fatal neurodegenerative diseases. This distinct characteristic sets them apart.
The Nature of Prions
The term “prion” is derived from “proteinaceous infectious particle,” highlighting their protein-only composition. Prions are an abnormal form of a normal protein called prion protein (PrP), found on the surface of cells in the central nervous system. The normal version is known as cellular prion protein (PrPC).
The disease-causing form, PrPSc (Sc refers to scrapie, a prion disease in sheep), has the same amino acid sequence as PrPC but a dramatically altered three-dimensional structure. This misfolded PrPSc lacks nucleic acid, meaning it contains no DNA or RNA. The normal PrPC typically contains flexible coils called alpha helices, while in the PrPSc form, some of these helices are stretched into flat structures known as beta strands. This structural change makes PrPSc resistant to degradation by cellular enzymes called proteases, which would normally break down proteins.
Mechanism of Prion Propagation
The core concept of prion propagation involves the abnormal PrPSc acting as a template. When PrPSc encounters a normal PrPC molecule, it induces the PrPC to misfold and adopt the abnormal PrPSc conformation. This process is a chain reaction, where newly formed PrPSc molecules can then go on to convert more normal PrPC molecules, leading to an exponential accumulation of the misfolded proteins.
The accumulation of misfolded PrPSc proteins leads to the formation of aggregates and amyloid plaques in the brain. This aggregation damages nerve cells and interferes with synapse function, ultimately causing neurodegeneration. The progressive brain degeneration results in characteristic sponge-like holes, or vacuoles, in the brain tissue, known as spongiform degeneration. This process leads to impaired brain function and the symptoms associated with prion diseases.
Common Prion Diseases
Prion diseases affect both humans and animals, manifesting as progressive, fatal neurodegenerative disorders. In humans, the most common form is Creutzfeldt-Jakob Disease (CJD). Variant CJD (vCJD) is a distinct form linked to bovine spongiform encephalopathy. Other human prion diseases include Kuru, historically seen in New Guinea due to ritualistic cannibalism, Gerstmann-Sträussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia (FFI), both rare genetic disorders.
Animal prion diseases include Scrapie, recognized in sheep for over two centuries, which causes affected sheep to rub against objects, leading to wool loss. Bovine Spongiform Encephalopathy (BSE), known as “Mad Cow Disease,” primarily affects cattle and was initially linked to feeding cattle with scrapie-infected sheep parts. Chronic Wasting Disease (CWD) is another significant animal prion disease found in cervids like deer, elk, moose, and reindeer, and has spread across North America and into other continents.
Transmission and Prevention
Prion diseases can be acquired through several routes: sporadic, inherited, or acquired. Sporadic cases, like most CJD cases, arise spontaneously without a known cause, accounting for 85% to 90% of all human prion diseases. Inherited forms result from genetic mutations in the PRNP gene, making the PrPC protein more likely to misfold. Acquired transmission typically occurs through exposure to contaminated tissue, such as during medical procedures (iatrogenic transmission) or by consuming contaminated meat products, as seen with variant CJD.
Preventing the spread of prion diseases involves several strategies. Strict sterilization protocols are implemented in medical settings, given that prions are resistant to normal sterilization methods like cooking, washing, or boiling. This includes proper handling and disposal of potentially infected tissues and medical equipment. Regulations regarding animal feed, such as banning the use of infected animal tissues in feed, are also crucial in preventing transmission among livestock, as seen with BSE. Additionally, individuals with suspected or confirmed CJD are advised not to donate organs or tissues to prevent iatrogenic spread.