Prions (Spongiform encephalopathy)

Spongiform encephalopathy can be broken down. Spongiform means sponge like, encephalo- refers to the brain, and -path refers to a disease process.

So spongiform encephalopathy is a disease where the brain tissue degenerates and healthy tissue gets replaced by clusters of tiny liquid filled, thin-walled cavities called cysts, making the brain look like a sponge.

The underlying cause of spongiform encephalopathy is the accumulation of misfolded proteins called prions.

First, let’s review a bit. Proteins are made up of a long string of amino acids, and the exact sequence of these amino acids is called the primary structure.

These long chains of amino acids can fold to form different shapes, like an α-helix which is a right-handed coiled strand and a ß pleated-sheet which is when the chain folds so that segments line up alongside one another.

Each protein can contain multiple α-helices or ß pleated-sheets.

Now, there’s a protein called Prion protein, or Prp, which is encoded by the PrNP gene.

This protein is 253 amino acid long and is made up of mostly α-helices.

It’s most commonly found on the cell membrane of neurons.

Although the function of Prp is unknown, it’s thought that it might play a role in synapses between neurons and the uptake of copper into the cell.

When a prion protein is misfolded, it changes from mostly having α-helices to having a lot of ß pleated-sheets.

This new abnormal protein is called a “prion”.

When the misfolded protein enters the cells of the nervous system and interact with the normal prion protein, it acts as a template and induces misfolding in the normal prion proteins.

These prions are also highly resistant to being broken down by proteases, which are the enzymes that break down abnormal proteins.

As a result, these misfolded prion proteins cannot be easily broken down, they cause normally folded proteins to misfold and become like them, and they have an affinity for the brain - they’re basically like little ß-sheet filled zombies.

The misfolded prions accumulate within the cell and they trigger apoptosis, which is programed cell death. This is done with the help of 14-3-3 protein which is an intracellular protein that promotes apoptosis.