Prion proteins are encoded by the Prnp gene, derived from the Prn gene family. This gene codes for a 254 amino acid protein, which, during posttranslational modification, is truncated to its wildtype 209 residue cellular prion protein (PrPC) form.1 PrPSc is the pathogenic form of PrPC, which primarily differs in secondary and tertiary structure. A protease resistant, 142 amino-acid pathogenic form, called PrP 27-30, is also sometimes derived from the cleaving of PrPSc.1 After posttranslational modifications, PrPC is then anchored extracellularly to the cell surface by its C-terminus to a glycosylphosphatidylinositol (GPI) anchor in a lipid raft.1 It also has two N-linked oligosaccharide chains. 1 Additionally, the protein can be found …show more content…
Another important interaction is with Bax, a protein in the Bcl-2 family, that is important in apoptotic pathways. PrPC is known to inhibit Bax activity, preventing apoptosis in fetal neurons.1 Other proteins that are known to interact with PrPC include, but are not limited to, the Grb2 signal transduction adapter protein, TREK-1 potassium channel, tubulin, N-Cell adhesion molecule, and synapsin 1b, which is involved in synaptic vesicle trafficking.1 Because of its broad physiological cellular involvement, PrPC has the potential to influence many cellular functions. Although there have been somewhat mixed results, some PrPC knockout mice have shown normal development, followed by neuronal decline, due to a lack of the Prnp …show more content…
Nuclear magnetic resonance (NMR) of concentrated PrPC solutions was used to determine its exact shape. Analysis revealed a secondary structure that includes one 4 amino-acid (AA) and one 3AA 훽-sheet, and one each of 11AA, 22AA and 28AA α-helices.1 Studying the PrPSc form has proven difficult because of its formation of disordered aggregates. The knowledge that we do have about this pathogenic form is derived from electron crystallography, and computer modeling, and reveals, while still having the same number of 훽-sheets and α-helices, a more heavily 훽-pleated sheet dominated structure.1 This change in conformation causes the PrPSc to be insoluble in non-ionic detergents, as well as resistant to degradation by proteinase K. PrPSc can either be formed by spontaneous conversion of PrPC to PrPSc, or by exposure of PrPC to PrPSc. The conformational conversion of the prion protein has been hypothesized as being related to the unstructured N-terminal domain, and specifically, a 21 nucleotide region termed the “toxic-peptide”, of PrPSc.1 This small region received its name because its introduction to other proteins induces 훽-sheet structured fibrils formation, and is known to damage the mouse hippocampus. Narrowing down the mutagenic segment of this peptide has lead researches to a small portion within the N-terminal domain, specifically in the hydrophobic-core, with the
Alu elements are a class of transposable genes found exclusively in the genomic sequences of primates. Averaging in lengths of approximately 300 base pairs, Alu elements are classified as being short interspersed elements, more commonly referred to by the acronym SINEs. These elements interject themselves into the DNA sequence by means of retroposition. Once established into the genome, Alu elements are considered to be stable, only rarely being subjected to deletion. Initial studies on the prevalence of Alu inserts within the modern human genome was calculated to be nearly 5% (Comas, Plaza, Calafell, Sajantila, & Bertranpetit, 2001), however, more recent research indicates that the actual percentage of various Alu elements account for nearly 11% of the DNA sequence (Deininger, 2011). Alu elements are of great importance to scientists, particularly to those who wish to study evolution, as well as, migrational patterns of early human populations.
...s to interfere with bonding to the receptors. The final possibility uses CNP, which downregulates the activation in MAP kinase pathways in the chondrocytes (4).
The MECP2 gene makes a protein, also called MECP2, believed to play a pivotal role in silencing, turning off or regulating the activity of other genes. The MECP2 mutation (change in the gene) causes the turn-off/regulatory mechanism to fail, allowing other genes to function abnormally(Rett Syndrome - NORD). Rett syndrome is a genetic disorder of developmental failure of brain maturation. This is thought to occur when subsets of neurons and their connections are disrupted during a dynamic phase of brain development. This deviation occurs at the end of pregnancy or in the first few months of life during the critical phases of synapse development. How mutations in MeCP2 lead to Retts is not well understood but is the focus of intense research.
The origin of CWD has yet to be determined (Sigurdson & Aguzzi, 2007). The infection was first noted in 1967 at a captive mule deer research facility. In 1978 pathologists recognized the TSE type brain lesions, also that CWD presented as a prion disease by the neuronal perikaryonic vacuoles, the accumulation of aggregated prion protein and prion infectivity in the brain. In the late 1970s and early 1980s the infection w...
PrP can occur in two forms- a normal cellular prion protein known as PrPc and a pathogenic misfolded conformer known as PrPsc. The abnormal PrPsc differs from the normal prion protein PrPc in both secondary and tertiary structure. PrPsc is principally rich in Beta sheet contents but PrPc is principally rich in alpha helical contents. Due to this difference of between the isoforms, prions are extremely resistant to certain decontamination systems. The Two tables below outline both human and animal diseases (2).
Autopsies of affected cattle reveal holes in the brain tissue that give it a spongy, or spongiform, texture. Similar spongiform diseases have been recognized in humans (for example, Creutzfeldt-Jakob disease or CJD) for over a century and in sheep (scrapie) for over 200 years. The cause of BSE is unproven, although there is strong evidence that prions, which may be infective proteins, are the agent. Other hypotheses suggest that prions work with an as yet undetected virus to cause the infection.
The prion diseases that Chronic Wasting Disease is related to are Creutzfeldt-Jakobs disease found in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapies in sheep (3,4). These diseases are grouped together because they share certain characteristics such as long incubation periods, spongiform changes that are associated with neural loss, and cause failure to induce inflammatory responses (Chronic Wasting Disease Alliance).
CP consists of a single domain with high α-helical content [4]. The N-terminal part this domain is surface exposed whereas the C-terminal region buried in the virion. Several experiments indicate the CP is an O-glycoprotein. Equal amounts of galactose and fructose residues are O-linked to an acetylated serine residue at the N-terminal region [2]. This mediates the formation of a structured...
Prions are pathogens, and cause infections, like viruses. Prions cause many neurodegenerative diseases, but are made up of harmless proteins found in mammals and birds. The proteins are not in their normal form though, and once they enter the human brain, can cause severe brain infections. One thing that makes them different from viruses, is the lack of nucleic acids, which means they have no genetic code. Once in the brain, they make normal proteins turn into abnormal ones, which then multiply, causing severe infection. Soon, holes appear in the brain that can only be treated by incineration. An example of a disease caused by a prion would be the Mad Cow Disease, or the human equivalent Creutzfeldt–Jakob disease. Prions are very dangerous. While some people can confuse prions and viruses, there are some ways to tell the difference.
Schulman, Joshua M., and David E. Fisher. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 28 Aug. 0005. Web. 24 Apr. 2014.
Prion Disease is an illness that many have not heard about. This is sad because many have died and are dying from this disease that doesn’t yet have a cure. “Prion Disease is a group of conditions that affect the nervous system in humans and animals… these conditions impair brain functions, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements particularly difficulty with coordinating movements (ataxia)” (Genetics Home Reference). This is basically the definition of what Prion Disease is and without going into depth it explains how it affects the person that is affected. “In t...
Creutzfeldt-Jakob Disease is an uncommon, deteriorating, consistently fatal brain disorder that is caused by prions. The symptoms of CJD are similar of Alzheimer’s but progress much faster. There are three variations of CJD, sporadic, familial, and acquired. All variations affect the brain the same way and have the same result of death. CJD is an untreatable and incurable disease.
In the past decade, the demand of performance from elite athletes has risen drastically. This demand brought about more injuries, in turn increasing the demand for quicker recovery times from surgery or from an acute injury in these top athletes. Doctors have discovered what they believe to be a helpful solution to the problem, Platelet-Rich Plasma Injections (PRP). These injections are to be administered directly into an athlete’s injured tendon. PRP is a process that essentially separates your blood through bone marrow, leaving part of it extremely strong. However, the reasons for the strength are due to it coming from the patient’s stem cells, bringing non positive attention to this new age treatment. Because this stronger, platelet-rich plasma contains your own IGF-1, which is a growth factor that helps you heal. The platelet-rich portion of the blood can be injected back into the body directly at the site of the injury, with the intent of a faster recovery time. What is to be determined is if the PRP injections work well enough to become a standard treatment method and if this treatment is morally acceptable.
During early childhood, there is a huge proliferation of connections between neurons, usually peaking around the age of two. The adolescent brain then cuts down the amount of connections, deciding which ones are important to keep and which can be let go. While there are various theories as to the molecular mechanisms by which pruning actually occurs, most agree that pruning is primarily carried out by a very motile form of glial cell, called microglia [1], and pre-programmed cell death (apoptosis). These microglia are thought to remove cellular debris and perform surveillance during the healing process of an injured brain, but in the healthy, developing brain they have a possibly more important function. If a synapse receives little activity, it is weakened and eventually deleted by microglia and other glial cells through a process called long-term depotentiation (LTD). After the synapse has been removed, the space and resources that it once used are taken by other synapses. These synapses are strengthened by long-term potentiation (LTP). These processes and various others take place throughout development, peaking at adolescence and reaching their base around the age of 21, and transform the brain to create more complex and efficient neuronal configurations.
Proteins are considered to be the most versatile macromolecules in a living system. This is because they serve crucial functions in all biological processes. Proteins are linear polymers, and they are made up of monomer units that are called amino acids. The sequence of the amino acids linked together is referred to as the primary structure. A protein will spontaneously fold up into a 3D shape caused by the hydrogen bonding of amino acids near each other. This 3D structure is determined by the sequence of the amino acids. The 3D structure is referred to as the secondary structure. There is also a tertiary structure, which is formed by the long-range interactions of the amino acids. Protein function is directly dependent on this 3D structure.