Prions – a protein’s evil twin.

Credit: Neuropathology

This is the brain tissue of someone with a prions disease. The holes show areas where the prions have destroyed cells.

Prions are non-living infectious agents. The other infectious agents include viruses (also non-living), bacteria, fungi and protoctista (living). Prions are relatively rare and aren’t talked about as much, even in biology lessons. 

What are prions? 

Prions received their name from Proteinaceous Infectious Particle. They are essentially mis-folded proteins. We have normal cellular prion proteins (abbreviated as PrPc). These normal functioning proteins are found in the cell’s plasma membranes and in the central nervous system. They have a particular function in the synapses between neurones and in protecting a cell. However, sometimes these proteins are manufactured wrong. A mis-folded PrPc is called a PrPsc. When they are manufactured wrong, they no longer function and they can also transform other normal proteins into prions.

How are proteins made? 

Proteins are essential components of our bodies. They form enzymes and hormones that we need to function. Proteins are coded for by our DNA. There are particular genes that code for a particular protein. A process called protein synthesis takes place.  

Credit: Microbe Notes

During protein synthesis, the DNA is transcribed into mRNA. Then the mRNA is translated into amino acids. Amino acids are the building blocks of proteins. When they join together (by peptide bonds) they form a protein.

Sometimes there are mutations (changes) in our DNA or sometimes mistakes are made during protein synthesis. This means that different amino acids are coded for. They then fold up to create a different shaped protein. The function of a protein is reliant on its shape, thus when a protein is misshaped it no longer works. That can be harmful to many metabolic processes that rely on enzymes and hormones. 

Our body does have ways to correct the misshaped proteins in a process known as chaperone catalysis. Chaperones detect abnormal shapes and try to fix them. But sometimes they miss some proteins and are left undetected. 

In terms of prions. We have a PRNP gene in our DNA which codes for 250 amino acids that fold to make the prion protein. If there are no mistakes, protein synthesis will produce a prion protein (PrPc). If there are mistakes a prion will be produced (PrPsc). If the prion protein is coded into the wrong shape, then our bodies have a problem. This is because the particular PrPsc is shaped so that protease (enzymes that breakdown proteins) can’t bind to them. As a result, the PrPsc are resistant to protease and can’t be broken down. They are able to transform other prion proteins into abnormal prions. So one prion will cause many others to turn harmful. Instead of replicating like other infectious agents, they just turn existing ‘good’ prion proteins into ‘evil’ prions.

Credit: Prion Alliance

What do the prions actually do?

Prions can build up to form plaques which disrupts synapse function and signals between neurones. The prions are so small that they can’t be seen unless in plaques under an electron microscope. Over a period of time, nerve cells will become damaged and lost. Tiny vacuoles in the brain will form to give a spongey appearance. Diseases caused by prions are often called Transmissible Spongiform Encephalopathies. Below is the brain of someone with severe/progressed CJD. CJD is a prion disease found in humans. You can see that there are gaps in the brain.

Credit: Neuropathology

As a result of these changes to the brain structure symptoms of prion diseases include:

  • Impaired brain function
  • Changes in personality
  • Changes in memory
  • Changes in behaviour
  • Intellectual Decline
  • Trouble standing/balancing

Alzheimers is also linked to prions or the build up of proteins called amyloid beta and tau. This is under research at the moment because Alzheimers has been different to other prion diseases in the way they develop. Alzheimers develops slowly but prion diseases usually cause death quite early on.

CJD

CJD is a disease called Creutzfeldt-Jakob Disease. It was quite prevalent in Britain during the 1990s. The outbreak began as Bovine Spongiform Encephalopathy (BSE) in cattle (also called “Mad Cow Disease”) but a human variant called CJD emerged. The disease was contracted through eating beef infected with prions. There are multiple types of CJD and all of them are relatively rare. Agriculture and medial procedures have been improved to ensure this doesn’t happen and the families infected in the 1990s have received compensation (although that will never make up for the man-made disaster). The types include:

  1. Variant CJD (vCJD) – Consuming meat from a cow that had BSE. This variant is what caused the outbreak. It can also be transmitted through the blood of an infected individual.
  2. Sporadic CJD – Caused by normal protein changes, where a prion protein gene has mutated or there has been a mistake in protein synthesis.
  3. Latrogenic CJD – This is exposure to the tissue of someone infected. A common medium of transmission is through medical/surgical equipment that has not be sterilised properly (particularly during brain surgery).
  4. Familial/ Inherited CJD – A rare genetic mutation that you inherit from your parent. The DNA codes for the wrong protein so the prion protein is misshapen.
Credit: European Centre for Disease Prevention and Control

On the graph you can see the grey lines, showing the cases of BSE and vCJD in the UK. There was a steep increase during the early 90s of BSE, and in the late 90s for vCJD. However, you can also see it has declined a considerable amount. Prions are still rare but they are very deadly with little advancements in medicine to combat them. They are so small and specific it is difficult to target them like we do for viruses and bacteria.

Ending on a joke I found on the internet: Why is it called a prion? Because protein got misspelled when it was folded the wrong way.

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