It’s time for a throwback! Do any of you remember that small section in our AP bio book that talked about the existence of pathogenic proteins? If not, allow me to offer a quick refresher. In nature, there are amyloids (malformed proteins) called prions with the ability to alter other proteins and disrupt their function. Prions are known for how they afflict the brain and cause diseases such as “mad cow” disease and just so happen to be indestructible. These proteins do however, have very long incubation periods that are necessary for their accumulation in the host. The length of time not only obscures the outbreak location but limits the ability to study them in the lab and understand how they work.
To begin dissecting these intriguing natural phenomena, let’s compare older versions of synthetic prions with the real deal. In 2009 scientists Stanley Prusiner (Nobel Prize receiver for the discovery of prions) and Gerald Stubbs, who is a lead authority on determining fibrous materials’ molecular structures, teamed up and headed an investigation in order to identify why their cultivated prions aren’t as infectious as ones bred in vivo. By way of X-ray diffraction, they concluded that cultivated prions were folded into a ladder-like shape while “natural prions have a more complex, three-sided cylindrical shape” (ScienceDaily, 2009). This shape disparity is the most likely cause of the differences in infectivity, for the anatomy oft defines the physiology. With that understood people have taken another step towards treating these immortal pathogens and can work towards cultivating more natural prions.
Reproduction of prion proteins (PrP) for testing is oddly not that complex. If you get a high enough concentration of normal proteins (PrPC), lipids, and polyanions (mostly RNA). With those ingredients and enough cycles of Protein Misfolding Cyclic Amplification (PMCA) one can create the malformed prion proteins (PrPSc). Although this is possible, it is much faster and more reliable to add some PrPSc beforehand so it can go about altering the other proteins. Inside PMCA the process of making prion proteins from normal ones follows a simple pattern: induce and stabilize misfolding of PrPC, add misfolded protein to an end of PrPSc, once prion polymer is long enough it fragments thus creating more prion proteins (National Center for Biotechnology Information, 2012). This process makes PMCA the PCR of prions! It also gives us the ability to study just how such a peculiar pathogen can have such an irreversible impact on the neural systems of this it infects.
The most curious part of all this is, why do these proteins seem to only damage the brain? Well they don’t exist solely in neural tissue. Prions have been found in the spleen, pancreas, kidneys, and liver and seem “to spread to the parts of the body being targeted by the immune reaction” (Nature, 2005). Spreading was found in an inflammatory response which suggests that in some way our immune systems aid in prion replication. And yet, no other afflicted organ suffers as the brain does.
PrP in the wrong part of a neuron can bind to Mahogunin, a protein that is essential for certain neurons’ survival. PrP is usually found on the surface of a cell and has the unique purpose of protecting cells, especially fetal neurons, from the apoptotic Bax gene’s effects (National Center for Biotechnology Information, 2007). Once it is in the cytoplasm though it forms clusters with Mahogunin, restricting its function and ultimately leading to the downfall of the cell. This could be amended “if PrP was confined to the surface of the cell, if the cells were provided with additional Mahogunin, or if PrP was prevented from binding to Mahogunin” (National Institute for Health, 2009). Which further implicates that even though PrPs may bond to other proteins, Mahogunin is most likely the most important one it alters.
With all of this the future may seem rather bleak with prions in it, but, fear not for they are very rare in nature. Not to mention that researchers are working through ways to deal with prions even with their seemingly immortal lifespans. We all have wonderful scientists to thank for collecting the data necessary to better understand these magnificent and deadly proteins. Data that may bring about a day in which prions no longer threaten life on Earth.