Prions and Prion Diseases

The word Prion is derived from protein and infection. It is a proteinaceous infectious particle that affects the CNS of many animals including humans. Prion diseases, or Transmissible Spongiform Encephalopathies (TSEs), are a family of rare progressive neurodegenerative disorders that are always fatal. The brain tissue of these patients obtained at autopsy appear to look like a sponge because of the presence of several tiny holes in the cortex (hence the name spongiform). The other distinguishable features of brain damage include neuronal loss, amyloid plaque formation and astrocytosis. Some examples of prion diseases in humans are Creutzfeldt-Jakob Disease (CJD) and Kuru, and in animals, the most common one is Bovine spongiform encephalopathy (BSE), also known as mad cow disease. The clinical symptoms in humans commonly include involuntary shaking, memory loss and depression in the early stages, and severe mental and physical disabilities in the later stages.
In contrast to all other known infectious agents that contain genetic material in the form of DNA or RNA, like viruses, bacteria, fungi, or parasites, prion diseases are unusual in that the infectious agent which transmits the disease is a misfolded prion protein called PrP. You can imagine how much controversy this discovery must have created in the scientific community at the time! The normal form of the protein (PrPc) is present in all cells, although its function is unknown. The misfolded protein (PrPSC) is insoluble and prone to forming clumps. These abnormally folded proteins recruit more PrPc in the host cell and convert them to PrPSC, setting off a chain reaction in a process called nucleation-polymerization.
How exactly this happens is not well understood. One hypothesis, called the "Protein X" hypothesis, is that an unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSC by bringing them together into a complex. It seems that PrPSC can travel from an infected cell to a naive cell either through the synapse or by spontaneous uptake of PrPSC from the extracellular space, which would explain how the disease spreads. It is this form of transmission, conformational change, and aggregation that leads to the disease.
Mechanism of disease progression through misfolded prion proteins.
Most cases of prion disease are sporadic, meaning they arise spontaneously for no known reason. The incidence of sporadic CJD, for example, is around one per million of the population per year and affects males and females equally. More rarely, prion disease is inherited, or acquired by medical procedures, transfusions, or contaminated food. The fact that these diseases can be transmitted horizontally is what makes them scary. An example is the disease Kuru, which reached epidemic levels through cannibalistic rituals in Papua New Guinea in the mid 20th century. Thanks to modern laws that now ban cannibalism, this disease has been prevented from recurring. However, a more recent epidemic of prion disease was the mad cow disease that claimed the lives of more than 150 people in the UK during the late 1990s, all of whom had eaten infected beef. To contain the outbreak, 3.7 million cattle were slaughtered in Britain! Since then, no cases have arisen from the consumption of contaminated meat. However, research suggests that prion diseases have very long incubation periods, from 5 to 50 years, raising the possibility of an epidemic of variant Creutzfeldt-Jakob Disease (vCJD) in the near future arising from many people who may have been exposed to infected beef in the UK during the 90s.

Saturday Night Live, NBC Studios
Recent studies are now starting to confirm the suspicion that common neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are also caused by prion-like mechanisms of propagation. Like prion diseases, all of these neurodegenerative diseases are associated with the accumulation of misfolded aggregates of proteins such as tau, amyloid-β (Aβ) or α-synuclein proteins. In my next blog, I will talk about the basis of these similarities and discuss some of the latest findings.

The Karate Kid, Columbia Pictures
In recent years, some hope has emerged in treating prion diseases. New approaches based on anti-prion antibodies that are capable of crossing the blood-brain-barrier and targeting cytosolic prions have been described1. Scientists are also currently working on identifying compounds that can bind a cavity in the PrPC and stabilize the conformation, thus preventing it from being converted to the harmful PrPSC 2. However, a lot more needs to be understood in terms of the mechanism of action and meaningful treatments will most likely require cocktails of drugs that quench the precursor protein, interfere with conversion of precursors into prions, and/or enhance the clearance of prions. Please let us know if you have any thoughts about prions and its diseases by contacting us at

South Park, South Park Digital Studios, LLC.
  1. A camelid anti-PrP antibody abrogates PrP replication in prion-permissive neuroblastoma cell lines
  2. Hot spots in prion protein for pathogenic conversion
  3. Prion Diseases
  4. Mad cows, cannibalism and the shaking death

Contributed by Mohar Chattopadhyay, PhD.
Login / Register
Forgot your password? Reset password?
Create an Account