We’ve all heard of Mad Cow disease (bovine spongiform encephaly) in the media. A few years back it was as big a sensation as bird flu and twice as scary. The colloquial understanding of the disease was poor: what it was, how humans (or cows) could get it, what should be done to curb its spread, and whether or not there was any treatment. This disinformation led to small-scale hysteria when it came to beef, with some countries (eg Japan) completely banning all beef from nations that were even suspected of having a “mad cow.” The beef industry as a whole took a hit, as pubic perception held that beef was now diseased, and could cause them to become demented or crazy.
Scientists rapidly discovered that “Mad Cow Disease” and its human counter-part Creutzfeld-Jacob’s Disease was caused not by traditional pathogens such as a virus or bacteria, but something as simple as a protein. Admittedly, this protein—called a prion—is actually anything *but* simple and studying prion diseases has been dangerous and slow to bear fruit. However, it is fascinating that a conformational change in a protein can wreak such havoc on the brain, quickly rendering it as porous as a sponge and its owner gradually more incapacitated.
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A prion is an infectious protein which are hypothesized to infect tissues and “reproduce” first by changing its own conformation, and secondly by inducing other benign proteins to do the same. The conformation that is induced is much larger than the normal protein confirmation should be (called an amyloid fold) and following aggregation of these prions, they can cause damage to tissues by expanding within them and causing “holes” to form.
Normal and diseased prions
Prion diseases are particularly nasty as these proteins are very resistant to denaturing or being broken down naturally, and there does seem to be a genetic component which alters the likelihood that someone would spontaneously develop a prion disease. However, the most common way people develop prion diseases is through transmission by infected animal byproducts. Diseases caused by prions (other than Mad Cow) include scapie, fatal familial insomnia, kuru (the laughing disease), and chronic wasting disease in deer.
The protein that prions are made of is found throughout the body normally(called PrPc), although what their non-disease function is is not yet known. These proteins are encoded by the PRNP gene, and mutations in this gene are responsibly for inherited prion diseases. The disease-state prion protein is called (PrPSc) and is resistant to proteases which would normally denature a protein and render it harmless. The theory of how prions become infectious to other proteins is detailed below.
First a disease-state prion (red) is either ingested or spontaneously created. As endogenous (naturally-occurring, shown in green) body prions come in contact with the diseased prion, they are forced to change their conformation to that of the diseased prion. This chain reaction eventually becomes exponential, with more and more diseased prions changing into an expanded conformation and aggregating, causing tissue damage. Note that this theory, while the most widely-held, is suspected, but not confirmed. Another hypothesis (the Protein X hypothesis) suggests that another unknown protein mediates the conversion of normal prion to diseased prion, however this enabler has yet to be found.
As mentioned, sometimes diseased prions are ingested from already-infected tissue. Kuru and Creutzfeld-Jakob disease are both transmitted this way, by eating the meat or brains of infected animals or people. Kuru was identified in a tribe that often ate the brains of defeated enemies as a ritual, however it had the unfortunate by product of spreading this disease. While proteins are usually broken down and digested in the gut, prions resist digestion and remain intact. Furthermore, they are not normally absorbed into the intestinal wall but rather pass into the Gut Associated Lymphoid Tissue (GALT) and then into the body’s main lymphatic system. From there, it is a short trip to the brain where they make a lethal home as the chain reaction described above begins.
In regards to Mad Cow, the few human cases that resulted were due to eating beef (or brains) of cows with diseased prions. This transmission event is quite rare, although one of the reasons that diseased prions were able to propagate through cattle populations is due to the practice of grinding up sick livestock for food for other cows. This had the effect of spreading mad cow at a much faster rate than would have been expected. Mad cow/Creutzfeld Jakob disease is always fatal and its symptoms are progressive dementia and loss of motor control.