Prions – The Killer Proteins

Prions are infectious agents those are composed primarily of proteins. To date, all such agents that have been discovered propagate by transmitting a misfolded protein state. Prions are proteins that are unique in their ability to reproduce on their own and become infectious. The protein itself does not self-replicate and the process is dependent on the presence of the polypeptide in the host organism. The misfolded form of the prions proteins have been implicated in a number of diseases in a variety of mammals.

All known prions diseases affect the structure of the brain or other neural tissue. They can occur in two forms called PrP-sen and PrP-res. It has been proposed that neurodegeneration caused by prions may be related to abnormal function of PrP-res. However, the physiological function of the prions proteins remains a controversial matter. There is evidence that PrP –sen may have a normal function in maintenance of long term memory. It has also been indicated that PrP-sen expression on stem cells is necessary for an organism’s self-renewal of bone marrow .

Virtually all neurodegenerative disorders involve abnormal processing of neuronal proteins. The aberrant mechanism can entail a misfolding of proteins; often accumulate because the cellular mechanisms for removing them are ineffective. The particular protein that is improperly processed determines the malfunction of distinct sets of neurons and thus the clinical manifestations of the disease. All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death. This stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult.

Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form amyloid fold, which disrupt the normal tissue structure. This disruption is characterized by “holes” in the tissue with resultant spongy architecture due to the vacuole formation in the neurons. While the incubation period for prions diseases is generally quite long, once symptoms appear the disease progresses rapidly, leading to brain damage and death. Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioral or personality changes.

Prions Diseases

The following diseases are caused by prions in different animals:

Classic Creutzfeldt-Jakob disease (CJD; human): The most prevalent of the spongiform diseases occurs spontaneously in  out of a million people. Usually strikes people age 50 to 75. Dementia, muscle twitching, vision problems are the most common symptoms.

Fatal Familial Insomnia (FFI; human): All cases are inherited mutations in the PrP gene. Usually effects people at age of 36 to 61. It is marked by disruption of sleep/wake cycle leads to coma, then death.

Kuru (human): Struck members of the Fore tribe in the 1950s and 1960s. Muscle weakness, loss of coordination, tremors, inappropriate episodes of laughter or crying. It is transmitted by ritual cannibalism as part of funeral ceremonies of fore tribe.

Scrapie (goats, sheep): Occurs as infection in genetically susceptible sheep. There is no evidence of spread to humans.

Bovine Spongiform Encephalopathy (BSE; cattle): Also known as “Mad Cow Disease” because infected animals act strangely and can be aggressive. There is still much debate in the scientific community regarding how BSE is spread. At the present time, BSE is thought to be spread in tissue from the central nervous system (brain, spinal cord) as well as distal ileum, some of which can be present in meat and bone meal. BSE is not spread by animal-to-animal contact. In other words, an animal infected with BSE cannot infect another animal with which it is penned or pastured.

Chronic Wasting Disease (deer, elk): It is Infectious disease in wild deer and elk primarily in the western United States. Infected animal has Drooling, difficulty swallowing, weight loss.

Of all the laboratory research on neurodegenerative diseases, the studies that led to the discovery of prions have yielded the most unexpected findings. The idea that a protein can act as an infectious pathogen and cause degeneration of the central nervous system. The concept of prions not only has provided an explanation of how a disease can be both infectious and genetic, but has also revealed hitherto unknown kinds of neurologic diseases. Ongoing research may also help determine whether prions consisting of other proteins play a part in more common neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. There are some marked similarities in all these disorders.


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Image via Fortish / Shutterstock.

Zaid Ahsan, MSc

Mr. Zaid Ahsan holds a commercial pilot license in India and Philippines. He earned a MSc from Jamia Millia Islamia in biotechnology. Although a published scholar in molecular biology, his present research interest is aviation medicine.
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