Prions in the Body and Creutzfeldt-Jakob Disease (CJD)
What Are Prions?
Prions are misfolded proteins that can cause some very serious diseases. Unfortunately, their formation and behaviour isn't completely understood. Researchers are trying to unlock the mysteries of these small but potentially deadly particles.
The normal proteins in our body are essential molecules with complex, folded shapes. The shape of a protein enables it to do its job. If a protein is folded incorrectly or becomes unfolded it can no longer function. A prion (pronounced "preeon") is a misfolded protein with a special ability. It can change other protein molecules into prions. These can then alter the shape of even more proteins in a chain reaction.
Prions are the causal agents of some horrible illnesses known as prion diseases. These often progress rapidly once symptoms appear and (at the moment) are always fatal. The most common prion disease is Creutzfeldt-Jakob disease, or CJD. A variant of this disease has appeared in people who have eaten contaminated meat from a cow suffering from bovine spongiform encephalopathy, or BSE. BSE is a prion disease in cattle. It's also known as Mad Cow disease.
Pathogens: Infectious Agents That Cause Disease
Most infections are caused by viruses, bacteria, and fungi, including yeasts. Infectious agents that cause disease are known as pathogens. Like human cells, pathogens contain DNA (or, in the case of some viruses, a similar chemical called RNA). DNA and RNA belong to the nucleic acid family. Nucleic acids contain genes. The genes contain a code that controls a pathogen's structure and behaviour and enables it to cause an infection.
A prion consists of protein and has no nucleic acid or genetic code. The discovery that prions could reproduce in our body and cause disease was at first very hard for scientists to accept. Although they now know that this happens, they still have many questions about how and why prions form and about how they function.
Difference Between Normal Prion Proteins and Prions
Prion proteins are common in our body and occur in two varieties. One is a normal and necessary part of our cells while the other (the prion) is dangerous. Prions not only transform useful proteins into harmful ones but also form protein clumps.
Cellular or Normal Prion Proteins
A cellular prion protein (PrPc) is a normal constituent of cells and is folded correctly. Cellular or normal prion proteins are located throughout the body but are especially abundant in the brain. They seem to be very important in the life of cells, although their exact function isn't known. They may play a role in preventing cells from being damaged.
Abnormal Prion Proteins or Prions
An abnormal prion protein that is folded incorrectly and has the ability to cause other proteins to become misfolded is often known as simply a "prion". It's symbolized by PrPsc. The "sc" stands for scrapie, the first prion disease to be discovered. Scrapie damages the nervous system of sheep.
Prion Formation and Activity
How Are Prions Made?
Prions may appear in our body for several reasons.
- They may enter the body from another organism.
- They may be made in our bodies due to altered genes. Genes contain instructions for making proteins. Some inherited genes may contain a mutation (a change in a gene) that alters the structure of the gene and causes it to code for a misfolded prion protein, or prion.
- Normal prion proteins may spontaneously change into prions.
Transmissible Spongiform Encephalopathies
Prion diseases are quite rare in humans (as far as we know), but they are very unpleasant for the sufferers. They affect the brain more than any other body part and cause neurodegeneration.
Prion diseases are also known as Transmissible Spongiform Encephalopathies, or TSEs. They are known as spongiform diseases because they cause nerve tissue to break down and make the brain look as though it has spaces resembling the pores of a sponge.
Classic Creutzfeldt-Jakob Disease, or CJD
About 1 in a million people develop Creutzfeldt-Jakob Disease or CJD every year. In the United States, the incidence of CJD is about 200 to 300 cases per year.
Symptoms of CJD include a personality change, depression, vision problems, loss of muscle coordination, balance problems, jerky movements, slurred speech, memory loss, and impaired thinking and judgement. Eventually patients are unable to walk or feed themselves and lose awareness of their surroundings. Death is usually due to pneumonia, respiratory failure, or heart failure.
Since there is no cure for CJD, the goal of treatment is to relieve pain and make the patient feel as comfortable as possible. Research into finding an effective treatment or cure is continuing.
More Information About Creutzfeldt-Jakob Disease
Types of Creutzfeldt-Jakob Disease
There are three main types of classic Creutzfeldt-Jakob Disease.
- Sporadic CJD is the most common type. It develops when normal prion proteins in the patient's body spontaneously change into abnormal ones. The cause of this change is unknown. The prions that are made can transform other normal prion proteins.
- Sporadic CJD generally develops in people aged 45 or older. The disease usually lasts for six or seven months after the first symptom appearance, but some people have died after only a few weeks while others have lived for a year or more.
- Familial CJD develops due to inherited genes. The genes produce abnormal prion proteins in people aged about 50 or older. This form of CJD is much rarer than the sporadic form.
- A very rare disease called iatrogenic CJD is spread by a transplant of contaminated tissue from an infected person or by the use of contaminated surgical equipment.
BSE and Humans
Variant Creutzfeldt-Jakob Disease or vCJD
Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease are both prion diseases. Although the diseases have similar names, there are major differences between them.
- vCJD was discovered in the United Kingdom in 1996. It's a relatively new disease compared to CJD, which was discovered in 1920.
- All people who have developed variant Creutzfeldt-Jakob disease have lived in a country inhabited by cows with BSE. CJD hasn't been linked to BSE.
- Researchers believe that with the exception of three people, everyone to date who has become ill with vCJD became infected by eating contaminated beef. The three exceptions are thought to have become infected by receiving contaminated blood during a transfusion.
- Cow meat is the muscle of a cow. It can become contaminated with BSE prions when material from the brain or nervous system enters the meat. This could happen when processing equipment cuts through the spinal cord and then touches the meat, for example.
- Median age of death from CJD in the United States is 68 while median age of death from vCJD in the United Kingdom is 28.
- Each disease causes specific differences in the appearance of brain tissue.
- The first symptoms of vCJD are generally psychiatric or sensory problems. The patient develops the dementia that is typical of CJD later.
- People with variant Creutzfeldt-Jakob disease tend to live for longer than patients with classic Creutzfeldt-Jakob disease (about ten to fourteen months for people diagnosed with vCJD and around six months for people with classic CJD).
Incubation Period for vCJD
In October 2013, an interesting report was published in the British Medical Journal. The researchers collected data which suggests that 1 in 2000 people in the UK could have the vCJD prions in their body, even though they aren't sick. The data was obtained by examining appendixes removed from people around the country.
The number of vCJD cases in the UK peaked in 2000 and has fallen since then. Prion diseases seem to have an incubation period, which sometimes lasts for many years. During the incubation period no symptoms are present. Once the symptoms appear, the disease progresses rapidly. Some researchers suggest that vCJD might have an incubation period of about ten years, given that UK cases peaked about ten years after a recent BSE outbreak. Others suggest that the incubation period may be much longer.
The data described in the British Medical Journal is interesting, but scientists are cautious about their interpretation of the data. They say that infected people could remain asymptomatic for the rest of their lives. On the other hand, the prions could be in their incubation period and the infected people could eventually develop a prion disease. Not enough is known about prion biology to predict the outcome of the infection.
Gene Mutations and Prion Formation
Prion biology is fascinating and important. Even though the diseases caused by prions are quite rare, they are devastating for patients and their families. In addition, some other serious human disorders involve misfolded and misbehaving proteins and seem to operate in a similar way to prion diseases. These disorders include Alzheimer's disease and Parkinson's disease. Understanding prion diseases could help us to understand these health problems and even to treat them more effectively.
It may be that the effects of prions in our bodies are more widespread and common than we realize. We certainly don't understand the biology of the particles very well yet. For example, a few experimental drugs have been created that slow prion replication in the lab. A 2013 report described the apparent development of drug resistance in prions. Drug resistance normally develops in cells with nucleic acid, such as bacterial cells. The puzzle of how it could develop in protein molecules is one of the many aspects of prions that needs to be explained. There is still a great deal to learn about these mysterious particles and their role in health and disease.
Creutzfeldt-Jakob Disease Facts from the NIH (National Institutes of Health)
Variant Creutzfeldt-Jakob Disease Information from WHO (World Health Organization)
Prions in the Appendix from nature.com
Appearance of drug resistance in prions from Scientific American
© 2013 Linda Crampton