Prions: Proteinaceous Infectious Particles and Their Diseases
This paper examines prions — proteinaceous infectious particles — as the proposed causative agents of a family of fatal neurodegenerative disorders known as transmissible spongiform encephalopathies (TSEs). Beginning with the discovery of prions by Stanley Prusiner and the foundational work of Carleton Gajdusek, the paper traces the biology of normal and abnormal prion protein conformations, explains how misfolded PrPSc propagates neurodegeneration, and surveys specific diseases including Creutzfeldt-Jakob Disease, kuru, fatal familial insomnia, and bovine spongiform encephalopathy. It also addresses scientific skepticism of the prion hypothesis, diagnostic approaches, and the current state of treatment and research into antibody and gene therapies.
- Introduction to Prions and Their Discovery: Definition, discovery, and early history of prion research
- Biology of Normal and Abnormal Prion Proteins: Protein folding, PrPC vs. PrPSc, and neurodegeneration mechanism
- Types of Prion Diseases: CJD, kuru, FFI, GSS, and BSE described
- The Prion Hypothesis and Scientific Debate: Evidence for and against the prion hypothesis
- Diagnosis of Prion Diseases: Diagnostic tests including MRI, EEG, and biopsy
- Treatment and Future Research Directions: Current symptom management and antibody or gene therapy research
✍️ How to write this paper — guide, tools & examples ▾
What makes this paper effective
- The paper builds understanding progressively — from molecular biology (protein folding, PrPC vs. PrPSc) to clinical presentation, diagnosis, and treatment — giving readers a coherent conceptual arc.
- It presents both sides of a genuine scientific controversy, acknowledging skeptics of the prion hypothesis and their evidence, which demonstrates intellectual balance.
- Historical context is well integrated: the contributions of Gajdusek and Prusiner are woven into the scientific narrative rather than treated as isolated biographical facts.
Key academic technique demonstrated
The paper uses comparison across multiple diseases (kuru, CJD, BSE, FFI, GSS) to establish a pattern of shared pathology, which is a classic technique in biomedical writing for validating a unifying hypothesis. This cross-disease evidence-gathering mirrors how Gajdusek and Prusiner themselves built the prion hypothesis from seemingly disparate clinical observations.
Structure breakdown
The paper opens with a definition and historical background, moves into molecular biology, then catalogs the main prion diseases before addressing scientific controversy. It closes with clinical sections on diagnosis and treatment. This structure — from mechanism to disease to debate to clinical application — is characteristic of a well-organized biomedical overview essay at the undergraduate level.
Introduction to Prions and Their Discovery
Recent cases of Mad Cow Disease have focused public attention on prion diseases and the small proteins believed to cause them. The scientific community has been slow to recognize this mechanism of disease, since prion-caused encephalopathies can demonstrate diverse symptoms and share characteristics with other disorders, such as dementia.
Prions, as the acronym suggests (Proteinaceous Infectious Particles), are small proteins typically expressed in brain tissue that may exist in a normal or abnormal shape. The prion protein is encoded by a gene found on human chromosome 20. Usually, the prion protein is translated in neural tissue, folds into its normal conformation, carries out its cellular role, and is eventually degraded by enzymes. The abnormal prion, however, folds differently from its normal counterpart. This different shape makes it more difficult to degrade and leads to the brain damage seen in patients with prion diseases.
The discovery of prions is credited to Stanley Prusiner, a professor at the University of California, San Francisco School of Medicine. Professor Prusiner coined the term "prion" to describe an apparently new phenomenon of disease transmission and was awarded the Nobel Prize for Medicine in 1997. Prion disease, however, has been documented for centuries in various species. Scrapie, a disease affecting sheep and goats, has been recognized since the 1700s. Similarly, bovine spongiform encephalopathy (BSE) is a progressive neurodegenerative disease that affects cows. Prusiner won the Nobel Prize for his "prion hypothesis," originally published in 1982, although investigation into human prion diseases dates back decades earlier.
Carleton Gajdusek, an American pediatrician, was instrumental in laying the groundwork for Prusiner's prion hypothesis. In the 1950s, Gajdusek studied a rare disease — kuru — that was afflicting the Fore tribe of New Guinea highlanders. He found that the devastating neurodegeneration exhibited by certain members of the Fore tribe could be traced to ritual cannibalism. Autopsied brains of the victims showed a similar type of brain damage to the brains of sheep affected with scrapie. Gajdusek also studied patients with Creutzfeldt-Jakob disease (CJD) and noted that the brain tissue had a similar sponge-like appearance. Based on these apparently diverse diseases, Gajdusek postulated that a new type of infectious agent was responsible. Although the term "prion" did not come into use until the 1980s, Dr. Gajdusek was awarded the Nobel Prize for Medicine in 1976 for the work that linked these disparate afflictions.
Biology of Normal and Abnormal Prion Proteins
The infectious nature of the prion protein is based upon its conformation once it is translated and folded. Normally, the protein product of the prion gene folds into a structure consisting primarily of alpha-helix coils. This shape is known as PrPC (prion protein, cellular) and allows the protein to function normally. Although the precise role of the normally folded prion protein is not fully understood, it is believed to play a role in synaptic message transmission in brain tissue. When the protein has fulfilled its purpose, it is degraded by brain tissue enzymes.
The way in which a protein folds after being translated is critical to the protein's function. This means that the same amino acid sequence can have devastating consequences if it folds in a different manner. In the case of the abnormal prion protein, the abnormal conformation consists of more beta-pleated sheets than alpha-helices. This abnormal form is denoted PrPSc (prion protein, scrapie). The different shape of the infectious prion protein makes it resistant to degradation by enzymatic function. The protein builds up in brain tissue, damaging neurons and causing the sponge-like (spongiform) appearance that is typical of prion disease-infected brains.
Prion diseases progress because the abnormally folded proteins can "infect" nearby normal proteins and cause them to refold into the abnormal conformation. In this way, a small amount of abnormal prions can convert other proteins and lead to progressive neurodegeneration.
Types of Prion Diseases
The most common human prion disease is Creutzfeldt-Jakob Disease, a progressive neurodegenerative disorder that can arise randomly ("sporadic CJD") or as a result of contamination with infected tissue. Because prions are proteins, and proteins are coded for by genes, some prion diseases can be inherited. A small percentage (10–15%) of CJD cases are attributable to an inherited gene mutation. A similar mutation is responsible for other, less common prion diseases. A fatal form of insomnia caused by progressive prion brain damage — fatal familial insomnia (FFI) — is caused by a mutation in the prion gene, as is Gerstmann-Sträussler-Scheinker disease (GSS), an affliction similar to CJD. The umbrella term for this family of prion diseases is transmissible spongiform encephalopathies (TSE).
CJD, the most common prion disease, was named for the German psychiatrist Creutzfeldt and neurologist Jakob, who first identified it in 1920. The overall incidence of this prion disease is one in one million (Prusiner, 2003). Approximately 85% of CJD cases arise sporadically, possibly when a normal prion protein misfolds and infects surrounding tissue. The remaining cases occur as a result of an inherited mutation in the prion protein or are acquired through contact with infected tissue. These acquired cases have been caused by transplants from affected cadavers — such as corneas and dura mater — as well as infection due to contaminated surgical instruments. Approximately 100 cases of CJD were caused by a growth hormone treatment the victims received as children that was harvested from human cadavers.
Transmissible spongiform encephalopathy has a long period of dormancy — sometimes decades — before symptoms appear, often in middle age. The typical age of onset ranges from 45 to 75 years old, and once symptoms appear the disease progresses rapidly. CJD victims usually die within six months of the appearance of symptoms. Because prion disease is a progressive, degenerative brain disease, tissue damage may cause personality changes and memory problems, followed by impaired motor control and difficulty communicating. In many cases of CJD, symptoms are mistaken for dementias such as Alzheimer's disease or other neurodegenerative diseases such as Parkinson's disease or ALS. These similarities between CJD and other, more common diseases present a significant challenge in diagnosing prion diseases.
References
Inherited prion disease. (n.d.). Retrieved April 21, 2004, from http://www.st-marys.nhs.uk/specialist/prion/factsheets/inheritedpd.htm
Kightly, R. (n.d.). Prion replication and spread at the cellular level. Retrieved April 21, 2004, from Mad Cow Disease Images & BSE Pictures Web site: http://www.rkm.com.au/BSE/index.html
Novak, G. (n.d.). Prions and junk science. Retrieved April 22, 2004, from Science Criticism Web site: http://www.nov55.com/prin.html
Prusiner, S. (2003). The prion diseases. Retrieved April 22, 2004, from Prions Web site: http://www.albany.net/~tjc/prion.html
Roos, R. P. (2001). Controlling new prion diseases. New England Journal of Medicine, 344, 1548–1551.
Sander, D. (2004). Prions. Retrieved April 21, 2004, from All the Virology on the WWW Web site: http://www.tulane.edu/~dmsander/
Secko, D. (2003). Preventing prion disease progression. Retrieved April 21, 2004, from The Scientist Web site: http://www.biomedcentral.com/news/20031103/02/
Somerville, R., & Bolton, D. (2000). Do prions exist? Retrieved April 21, 2004, from Nova Online Web site: http://www.pbs.org/wgbh/nova/madcow/prions.html
Tritz, G. (2000). Prions and viroids. Retrieved April 22, 2004, from Molecular Microbiology Web site: http://www.kcom.edu/faculty/chamberlain/website/lects/Prions.htm
Winklhofer, K., Heske, J., Heller, U., Reintjes, A., Muranyi, W., Moarefi, I., & Tatzelt, J. (2003). Determinants of the in vivo folding of the prion protein. Journal of Biological Chemistry, 278(17), 14961–14970.
Wong, J. (2003). Researchers discover possible diagnosis, treatment, vaccine for mad cow, prion diseases. Retrieved April 21, 2004, from Eurekalert Web site:
Create your account
Always verify citation format against your institution’s current style guide requirements.