Prions are infectious protein agents that cause aggregation of the peptide PrPC and form large amyloid fibrils. These fibrils resist proteoysis and can have a detrimental effect of the functionality of cells and ultimately cause their death. (3). Misfolded PrPC will form stable aggregates denoted as PrPSc. PrPC is a soluble protein that is present in all organism whose function is still not totally clear (3). When PrPc converts to PrPSc there is an increase in the number of β sheets in the protein, which can allow for interaction and stacking of other misfolded PrPSc proteins, causing an amyloid fibre to form (5).
One of the most relevant prions with regards to human health is Creutzfeldt-Jakob Disease (CJD).CJD is a neurodegenerative disease that causes rapid deterioration over a few months (1).Degeneration can lead to personality changes, depression, memory loss, blindness and many other symptoms (1).Before the identification of variant CDJ, sporadic cases of CJD made up 85% of the CJD cases, followed by familial CDJ causing 5-15% of cases, and the remaining cases contributed to iatrogenic CJD. I will be primarily focused on iatrogenic CDJ and variant CDJ.
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Once a prion enters the neurons, it can cause degeneration by aggregating with normal
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).
There is now strong scientific suspicion that the agent responsible for the outbreak of prion disease in cows, bovine spongiform encephalopathy (BSE or 'mad cow' disease), is the same agent responsible for the outbreak of vCJD in humans. Variant CJD (vCJD) is not the same disease as classic CJD It has different clinical and pathologic characteristics. Each disease also has a particular genetic profile of the prion protein gene. Both disorders are fatal brain diseases with unusually long periods measured in years, and are caused by a transmissible agent called a
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
BSE is caused by the misfolded prion protein known as PrPsc which originated from PrPc protein. Prion proteins are formed when PrPc becomes a misfolded polypeptide chain – a change in the shape of the protein. PrPsc influences the folding of PrPc multiple times leading to aggregates to form fibers that
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.
This week may be the last week I write to you. In my last letter to you, you may have noticed that I seemed depressed and not like myself. I wasn’t completely truthful in that letter. I’m not just having a bad day, I’m diseased with an incurable, fatal disease.
The prion protein (PrP) is unusual in that it has two stable isoforms. The cellular or normal form of the prion protein is termed PrPC, while the disease form is termed PrPSC. Sharing the same sequence of amino acids, or primary structure, PrPC and PrPSC differ in their secondary, tertiary, and quaternary structures. The normal prion protein has N- and C-terminals, three alpha helices, and two beta sheets (Soto, 2006, 40). Its function is still not completely understood. However, scientists have found evidence that point to various possibilities. 1) Because most PrPC are located in lipid rafts, membrane structures involved in signaling, it is suggested that PrPC may also be a mediator in neuroprotective signaling pathways. 2) Interaction between PrPC and Bcl-2, a ligand involved in protecting neurons from apoptosis, suggests the possibility that PrPC may be an antiapoptotic protein. 3) PrPC has also been linked to copper metabolism in the brain. In one particular study, PrP knockout mice, or mice that were genetically altered to not express PrP, were found to have lower levels of copper in their brains and higher levels in their serum (Soto, 2006, 42). However, in other studies with PrP knockout mice, most of the animals did not display any obvious disorders, and those that did were found to have been affected by the increase in concentration of another protein known as doppel.
A prion is a pathogen that lacks nucleic acid. Though they cannot reproduce and are not susceptible to procedures that break down the nucleic acid, they can replicate by stimulating normal cellular prion protein to refold from normal prion protein to abnormal prion protein. They replicate in neural tissue causing degeneration and death. The actual process of how normal prions convert to abnormal prions remains unknown.
However, differing from the other diseases, Prion sometimes spreads through contaminated meat. In the article “Prion Diseases” it shows meats that have mad cow disease can cause prion disease. Intake of unhealthy meat is not infectious since the spread is not direct. Moreover, like Alzheimer’s, transferals through medical procedures may cause the gain of Prion Disease. Prion disease can be the result of a transfusion with a person with the disease. Furthermore, many things may take a toll on the spread of Prion disease, but it is not
Neurodevelopmental disorders are characterized by impairments of the growth and development of the central nervous system as they occur by origin, or during infancy and childhood, inhibiting functions that affect emotion, learning, self-control, motor skills, and memory. Specific disorders within this spectrum include but are not limited to, fetal alcohol syndrome, autism, Tourette syndrome, fragile-X syndrome, Down syndrome, ADHD, Mendelsohn’s syndrome, and schizophrenia. Neurodevelopmental disorders stem from many causes, ranging from chromosomal deficiency, genetic and metabolic diseases, immune disorders, infectious diseases, physical trauma, and nutritional, toxic, and environmental factors (Bale, et.al., 2010).
Several different existing drugs have been created with intentions to treat prion diseases, to name a few, quinacrine and doxycycline have helped treat Prion Diseases. Although treatment is used in there has not been fully effective medication that completely eliminates the disease nor helps the victim recover completely. Antibodies against PrP could be one of the most potential treatments since they do protect against the prion protein our own body is creating. It is difficult for drugs to have an effect on prion diseased victims because the blood brain barrier only allows certain specimens to get through. Sporadic and genetic prion diseases in human begin in the brain inevitably forcing them to be untreatable because the immune system does
Alzheimer’s disease (AD) is a profoundly common form of degenerative dementia that is caused by neurofibrillary tangles and amyloid plaques accumulating in the brain (Sennvik et.al., 2000). The study of the human genome has elucidated gene variants; single nucleotide polymorphisms (SNPs) and mutations which affect the age of onset and the likelihood of developing AD. Understanding the causes of familial AD, the genetic risk factors for AD and the links between AD and other disorders; such as Down’s syndrome, will aid researchers in the diagnosis and treatment of AD.
Most often when people think of proteins, we do not think of them as being harmful or infectious agents. In fact we are generally taught that proteins are essential for organisms to function and to function correctly. However, there are indeed proteins that one could consider to be killer proteins. These proteins are called prions. Prions are a particularly interesting type of protein just in the fact that they have the ability to misfold on their own and also to become infectious agents. In simplest terms the prion proteins misfold, forming an abnormally shaped protein. These abnormal protein plaques then begin building up and forming clumps inside the brain which damage and destroy the brains neurons. This disease process progresses relatively
In this book, we highlight recent advances in the study of protein misfolding disorders and their protein targets, but we also describe how different organisms exploit the amyloid fold for the functional and dynamic assembly of biological structures.
A prion is a protein with a three-dimensional shape, as opposed to standard proteins. When a prion comes into contact with another protein, that protein transforms into another prion.