Understanding prion infections

Prions are particles solely made up of protein that can cause an infection in various hosts. These proteins are responsible for causing numerous diseases in both humans and animals. Examples include kuru, and Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, better known as mad cow disease, scrapie, and chronic wasting disease in animals. Prions are cause for concern and a problem that has to be addressed.

The term ‘prion’ was first used in 1982 and is a combination of the words ‘protein’ and ‘infection’. It is defined as a “proteinaceous infectious particle.” Being a protein, it cannot be classified as a living organism. However, it can infect a host just as well as a bacteria, virus, or a parasite. The proteins in prions are misfolded and they have the ability to transmit the misfolding to proteins that are correctly folded. The result is that healthy proteins in a host are converted to the misfolded proteins by prions. The process becomes an exponential growth as newly converted prions are also able to transmit the misfold.

The specific protein in the host that prions target are called PrPC and the infectious proteins are called PrPSc. PrPC is found in the cell membranes and plays a role in long-term memory.

Prion_propagation
source: https://en.wikipedia.org/wiki/File:Prion_propagation.svg

The image above shows PrPC being converted to PrPSc, the prion protein. The exact mechanism of this conversion is not fully understood yet. Eventually, prions cause neurodegenerative disorders by forming plaques within the central nervous system (CNS) that disrupts the tissue structure and activity. Again, not much is known about the progression of the disease or how exactly the neurons are affected.

The problem scientists’ face is that the infection has not been yet replicated in a laboratory setting to be studied. The study covered by the article puts forth a system through which the degeneration of the neurons can be studied. Neurons were isolated from the hippocampus of mice and allowed to mature for three weeks. During this time the neurons develop dendritic spines which are used for communication between neurons. The cultures were then exposed to brain material obtained from prion infected mice. It was immediately observed that the dendritic spines began to shrink whereas the neurons remained intact. The scientists hypothesized that this could potentially be one of the first steps of prion infection of the CNS.

A second set of experiments were conducted to observe if the prion infection was dependent on the PrPC presence in healthy cells. First, hippocampus neuron cultures from mice lacking PrPC were exposed to prions. The neurons were not infected and there were no changes observed on the dendritic spines. Then, neurons with mutated PrPC was exposed to prions. The mutation was at a site believed to be in a region needed for interaction with prions. These neurons were also immune to prions.

The research paper successfully accomplished two things: they developed a new method to study prion infection in vitro, and concluded that functioning PrPC was necessary for prion infection. These results can open doors for future investigation to identify the mechanism of prion infection and treatment options in both humans and animals. If the early shrinking of dendritic spines can be prevented then perhaps the progression of the disease can be halted.

I believe that this research is of great significance because it is the first to experimentally study the early effects of prion infection on neurons. The next steps would be conduct experiments en vivo. I believe that the experiments involving PrPC only serve the purpose to establish that PrPC is necessary for prion infection. It cannot have any treatment implications because lack of or mutated PrPC will be detrimental to the host since it has important functions.

The news article can be found here and the research paper can be found here.

 

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