Creutzfeldt-Jakob Disease Essay

Creutzfeldt-Jakob Disease: It happens when a prion protein misfolds itself, thus causing a “domino effect” which unfolds itself causing a malfunction.

Proteinaceous Infectious Particles, commonly known as Prions, are extremely rare misfolds of the protein PrPc, which cause fatally neurodegenerative diseases, and are theorized to be infectious only by the protein itself (U.S National Library of Medicine, 1998). This “protein-only theory” is still heavily debated today, as some scientists deny the theory, and there isn’t a significant amount of evidence on each side to qualify the theory or disprove it (Soto, C. 2011). The base “Prion” protein is encoded in the gene PRNP, while being non-infectious. Prions are most commonly found in human prion diseases, but they can also be in other animals in the form of Mad Cow Disease and Chronic Wasting Disease, classified as Bovine Spongiform Encephalopathies

Creutzfeldt-Jakob disease is a degenerative brain disorder that leads to dementia and ultimately death. Symptoms of Creutzfeldt-Jakob disease (CJD) sometimes resemble those of other dementia-like brain disorders, such as Alzheimer's, but Creutzfeldt-Jakob disease usually progresses much more rapidly.

Humans have to deal with many different diseases and the ones most disliked are the ones with no cures. Like cancer, transmissible spongiform encephalopathies have no cure, but they are more rare. These diseases are prion diseases which cause the brain to deteriorate. Prions are proteins that sometimes behave like viruses, which mean that they should have some form of nucleic acid, but since they don’t, they cause abnormalities. The nervous system contains many normal prions, but when an abnormal prion comes along, it transforms all the normal prions into abnormal ones. Bovine spongiform encephalopathy is found in cattle, but it can be transmitted to humans.

     Mad Cow Disease, scientifically referred to as (BSE) Bovine Spongiform Encephalopathy, is a disease that affects those humans who eat the meat from infected cows. Mad Cow Disease is one of several fatal brain diseases called (TSE) Transmissible Spongiform Encephalopathy. (USDA) There was evidence of a new illness resembling the sheep disease scrapie. It was technically named BSE but quickly acquired the mad cow tag because of the way infected cattle behave. (CNN) In 1997, there was an award given to Stanley Prusiner, for concluding that a distorted protein called a prion was responsible for Mad Cow Disease, noted the long incubation period made it difficult to distinguish (Bryant).

In bovine spongiform encephalopathy (BSE), the disease is caused by the misfolding of proteins that cause proteins and peptides to develop a fibrillary structure. The PrPc is a correctly folded prion and the misfolded form is called PrPSc. BSE occurs when the normal PrPc come into contact with the toxic PrPSc and the normal prion takes on the shape of the PrPSc. The normal chaperones are unable to convert the PrPSc back to the normal form. The PrPSc now takes on the role of chaperone and the conversion of PrPc prions continue over and over. PrPSc, now being hydrophobic avoids the water of the inner cell and begin to accumulate and form plaques along the neuronal cell membranes. The aggregation of the prions on the cell membrane eventually lead to cell death which produces the sponge-like appearance in the brain of cattle infected with BSE (Thompson, 2014).

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal human neurodegenerative condition falling under the category of Transmissible Spongiform Encephalopathy (TSE) because of having characteristic of spongy degeneration of the brain that it causes and its ability to be transmitted. First it was described in the United Kingdom in March 1996 and it has been connected with exposure to a TSE of cattle known as Bovine Spongiform Encephalopathy (BSE) sometimes called Classical BSE, having been reported first in 1986 in the United Kingdom.

Creutzfeldt Jakob Disease (CJD) is a rapidly progressive form of Dementia. Early diagnosis is important because the underlying cause of Dementia may be treatable. It appears randomly with no apparent reason, about 10% of those who are infected receive the disease through heredity. The use of a computerized axial tomography scan (CT) can help rule out other problems like stroke or brain tumor. The most effective is a Magnetic resonance imaging (MRI), because it can reveal patterns of abnormal brain signals and characteristics of CJD. In rare cases a brain biopsy may need to be performed. A small piece of tissue is removed and it is examined by a Neuropathologist, usually an MRI is sufficient. When a symptom on set happens, individuals may develop confusion, depression, behavioral changes, impaired vision and impaired coordination. As the disease processes there may be a loss of memory, also infected individuals may develop neuromuscular abnormalities. In later stages of the disease, individuals may have further loss of physical, intellectual functions, a coma, and repeated infections of the respiratory tract. Some people have life threatening and life ending complications, that develop less than a year after being

The U.S. Department of Agriculture (USDA) has tested hundreds of thousands of cattle for BSE. Researchers believe that the infectious agent that causes mad cow disease is an abnormal version of a protein normally found on cell surfaces, called a prion. For reasons still unknown, this protein becomes altered and destroys nervous system tissue (brain and spinal cord). There exists strong epidemiologic and laboratory evidence for a causal association between a new human prion disease called variant Creutzfeldt-Jakob disease (vCJD) that was first reported from the United Kingdom in 1996 and the BSE outbreak in cattle (http://www.cdc.gov). According to The National Creutzfeldt-Jakob Disease Surveillance Unit, by June 2014 it had killed 177 people in the United Kingdom, and 52 elsewhere. This essay will focus on the possible causes, effects, and treatment for this

The aggregation of prion proteins and their transmissibility from one cell to another has been shown to be evident (Cushman et al.; Goedert et al. 2010), therefore strongly suggesting that these events may play a role in pathogenesis for many diseases, including both AD and PD. While none of these diseases is infectious in an identical way as

While dysfunction of prion proteins remains the most widely accepted etiology of BSE, the USDA suggests there may be two other possible theories that could better explain the manifestation of BSE: the virino theory and the virus theory. However, both theories pale in comparison to the robust evidence in support of the prions theory. A major argument that works against both the virino theory and virus theory is that throughout several studies, the use of various treatments known to damage or inhibit nucleic acids have had no effect on the transmissibility of BSE. Interestingly, prion proteins lack nucleic acids – making them an excellent candidate as the infectious agent responsible for the development of bovine spongiform encephalopathy.

Many scientists hypothesize that protein dysfunction plays a role in the progressive damage and death of nerve cells. The nerve cells may be blocked from communication

Chronic Wasting Disease (CWD) is a fatal neurodegenerative transmissible spongiform encephalopathy (TSE ) found in some white tailed deer. CWD is associated with diseases such as Mad-Cow disease, Scrapie, and Creutzfeldt–Jakob disease. With well supported evidence it is hypothesized that CWD originated from Scrapie. The causation of CWD is an abnormal form of PrPcwd prion. This prion is a naturally occurring protein found in mammals. Prions lack genome and are highly resistant to degradation. Chronic Wasting Disease can be transmitted by direct contact between the animals and/or on resources such as salt licks.

Figure one: A simplistic schematic diagram depicting similarities between the PrPC protein and prion diseases, and the synaptic protein, α-syn and PD. Volpicelli-Daley et al. (2011) and Luk et al. (2012) studies illustrate a neuron-to-neuron transmissibility of α-syn drawing parallels between α-syn and the proteinaceous infectious particle pathogenic prion protein (PrPSc). PrPC consists of roughly 210 amino acids in length. PrPC comprises largely of an α-helical conformation and predominantly resides on the cell surface. When PrPC becomes misfolded, it acquires a high β-sheet content and assembles into rods that coalesce to form amyloid plaques. These aggregations dissipate throughout the brain, aiding neurodegeneration. Importantly, PrPSc is the sole component of the infectious prion and can cause disease in WT animals and humans. α-syn is a protein consisting of roughly 140 amino acids in length. It is a presynaptic protein that is involved in vesicular transport. On binding to cell membranes, α-syn acquires a largely α-helical conformation. When α-syn misfolds, it obtains a high β-sheet content and polymerises into fibrils that are related to the formation of Lewy bodies/neurites. Sole overexpression of α-syn can induce PD in WT animals and humans. There are significant parallels between PrPC involvement in Prion diseases and α-syn role in the formation of PD. This encourages the conception that PD is a “prion-like” disease. A

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that are thought to be caused by the misfolding of prion proteins. Prions are able to replicate in the absence of nucleic acids. TSEs include: scrapie, bovine spongiform encephalopathy, Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler-Scheinker disease, and Fatal Familial Insomnia. They can affect many different animals, including humans. Currently, there are no ways to diagnose, treat, or cure TSEs, as much more research is needed before these diseases are completely understood.