When I first learned about prions, I was struck by how quietly strange they are. They’re not bacteria or viruses, and they don’t carry any genetic information. They’re not even alive - yet they cause fatal, untreatable diseases in humans and animals. Instead, a prion is a protein that has folded into the wrong shape, and can persuade other proteins to do the same. This sets off a molecular-level cascade in the brain, one that scientists are still working to fully understand. So, how can something so small give rise to such devastating consequences?
Proteins are molecules found in every cell of your body — they carry out almost every biological function you can think of, from carrying oxygen in your blood to sending signals in your brain. Prion proteins, known as PrPᶜ, are one such protein. They are found throughout the human body, usually attached to the surface of cells. Their exact function isn’t fully understood, but scientists think they may help cells communicate with each other, particularly in the brain. Under certain conditions, however, these normally harmless proteins can misfold into abnormal shapes. When this happens, they become PrPˢᶜ, the infectious, disease-causing form of the protein. What makes prions so strange is that they can then trigger nearby PrPᶜ proteins to misfold as well, gradually spreading the abnormal shape. The two forms are chemically identical, and come from the same gene, the only difference between them is their structure. Because of this, we describe them as isoforms of the same protein. [1]
So, what actually happens when a healthy prion protein becomes an abnormal one? Proteins fold into different shapes, and these shapes determine how they behave. Two of the most common structures are α-helices, which look like spirals, and β-pleated sheets, which look like folded ribbons. [2] In normal PrPᶜ, α-helices are the more abundant shape, but when the prion misfolds into PrPˢᶜ, many of these helices are replaced with β-pleated sheets. This change in structure makes the prion unusually stable and able to spread its shape to other proteins. Once this misfolding begins, the next big question is: how does it start in the first place?
There are three main ways prion diseases can begin: sporadic, inherited, and acquired. Sporadic prion disease is the most common. It happens by chance, when a normal protein misfolds for reasons scientists still don’t fully understand. Inherited cases occur when a mutation in the PRNP gene increases the chances of the protein folding into the harmful shape. Finally, acquired prion disease happens when PrPˢᶜ enters the body from an external source.
The best‑known example of acquired prion disease is Bovine Spongiform Encephalopathy (BSE), or “mad cow disease”. This disease affects cattle, and was first recorded in 1986 when a cow in the UK was reported to be behaving strangely. The prion that causes this fatal neurodegenerative disease is the pathological prion PrPᴮˢᵉ. [3] BSE spread in the 1980s and 1990s when cattle were fed protein supplements made from infected meat, some of which contained the prion. This farming practice is now banned, and strict controls on animal feed mean that BSE is extremely rare today. [4]
Humans can also be affected, but the disease looks slightly different. Eating beef contaminated with the BSE prion can trigger a human form of the illness called variant Creutzfeldt-Jakob disease (vCJD). The prion involved is still PrPˢᶜ, but it has a slightly different shape, making it a different strain of prion. This is why the disease affects humans and cattle differently.
Despite their different origins, all prion diseases share one feature: they develop slowly. Misfolded prion proteins can build up in the brain for years — even decades — before symptoms appear. [5] Symptoms include rapidly developing dementia, balance and coordination problems, and involuntary muscle jerking. Unfortunately, there is no cure for these fatal diseases, but they are incredibly rare, and medication can help relieve symptoms. [6]
Although prion diseases are rare and currently untreatable, studying them has transformed scientists' understanding of how proteins behave in the human body. They have revealed that shape alone is enough to cause disease, opening new questions about other conditions involving the same misfolded proteins, such as Alzheimer’s and Parkinson's. Prions may be tiny and baffling, but they continue to push scientists to rethink what proteins do, and how such a small change to a molecule can have such a huge impact on the brain.
References[1] Colby, DW., Prusiner, SB. Prions. Cold Spring Harb Perspect Biol. (2011) [Accessed 2026 Jun 24]; 3(1):a006833. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3003464/
[2] Nature Education. Essentials of cell biology: Protein structure and function. (2010) [Accessed 2026 Jun 24] Available from: https://www.nature.com/scitable/ebooks/essentials-of-cell-biology-14749010/122996920/
[3] Wells GAH, Konold T, Arnold ME, Austin AR, Hawkins SAC, Stack M, et al. Bovine spongiform encephalopathy: a review. Vet Res. (2021) [Accessed 2026 Jun 24]; 52(1):70. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8583047/
[4] Centres for Disease Control and Prevention. Transmissible spongiform encephalopathies in humans. (2024) [Accessed 2026 Jun 24]. Available from: https://www.cdc.gov/prions/pdfs/tse-in-humans.pdf
[5] Prusiner, S. B. Prions. Proceedings of the National Academy of Sciences USA (1998) [Accessed 2026 Jun 24] Available from: https://www.pnas.org/doi/10.1073/pnas.95.23.13363
[6] Cleveland Clinic. Prion disease. (2023) [Accessed 2026 Jun 24] Available from: https://my.clevelandclinic.org/health/diseases/prion-disease
