The Importance Of Transfer Between Cells

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

You may use the lab manual, pre-lab lectures, and credible internet resources, however you may not use your cell bio lab classmates as a resource. You will most likely see this material again on the Final and I highly encourage you to work individually and seek help from myself or your TA. Plagiarism will result in an automatic zero.

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.

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).

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.

2. In a healthy cell floating in the cytoplasm are proteins we refer to as “chaperones” because they instruct or guide the folding of younger proteins. They guide them through the folding process resulting in perfectly structured protein. That performs its function as it should. When chaperones go bad aka Prions, as is the case in Bovine Spongiform Encephalopathy (BSE), we see the wide spread destruction that can occur when mutations in the folding occur. In Bovine Spongiform Encephalopathy the PrPsc protein acts as a chaperone and influences the PrPc protein it comes in contact with, to misfold which results in a new structure this new form iis hydrophobic (PrPsc). As these proteins form they aggregate with other PrPsc proteins. As the PrPsc proteins aggregate they trigger the neuron to self destruct which

Another mutated gene present in ADEOA patients is the PSEN1 gene (part of the y-secretase complex), which is responsible for the production of presenelin 1, which is meant to cut other proteins into peptides. The y-secretase complex also relates to the amyloid precursor protein by cutting it into smaller peptides thus aiding in the production of beta amyloid, and eventually the creation of amyloid plaques. Mutations in the PSEN1 gene “the most common cause of early-onset Alzheimer disease, accounting for up to 70 percent of cases” (Genetic Home Reference). Another mutated gene is the PSEN2 gene, similar to the PSEN1 gene. “One mutation replaces the amino acid asparagine with the amino acid isoleucine at position 141 (written as Asn141Ile or N141I). The other mutation changes the amino acid methionine to the amino acid valine at position 239 (written as Met239Val or M239V).” (Genetic Home Reference). These mutations appear to affect the production of amyloid precursor proteins and aids in the

PSEN1 and PSEN2 are polytopic membrane proteins (Davis et.al., 1998) that form the catalytic core in the protease γ-secretase (Francis et.al., 2002), which is responsible for the proteolysis of APP (Navivaeva & Turner, 2013). When there is a mutation at the loci for PSEN1 and PSEN2, located on chromosome 14 and 1 respectively, the activity of γ-secretase is altered resulting in changes in the proteolysis of APP and increased formation of Aβ (Qain et.al., 1998). Due to the increase of Aβ, amyloid plaques aggregate quickly causing early-onset of AD.

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

ALS usually starts in one part of a body (either a limb or bulbar region) and then slowly spreads to the rest of the body by non-cell autonomous or prion-like propagation. A presence of protein aggregates in the affected neurons was observed, but the nature of these aggregates

Prion-like proteins are normal proteins with similar prion-like domains which may also be involved in diseases of the brain or other organs. Seeded protein aggregation will lead to many more diseases of the brain. In contrast to prions being simple infection in yeast cells prion-forming proteins initiate cell process such as the central dogma. The prion-like proteins may not be widely pathogenic

The role of prions in BSE is to trigger proteins in the brain to fold abnormally. These prions are formed by abnormally folded protein that causes neurodegenerative conditions, similarly to that of Alzheimer’s disease. These misfolded proteins tend to clump together, or aggregate, because of their shape. This disease has no known cause but is generally associated with the ingestion of meat from cows who already have BSE.

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.

Cells are our bodies communicators: receiving and delivering information to our brains as to what we require for proper existence. These cells require nutrients as a source of energy to process these tasks. In single celled organisms, this process is quite simple; however this is not the case for our complex bodies. Multicellular organisms, such as us humans, carry out many functions in a day starting with , what appears to be, a simple task of acquiring nutrients and eliminating wastes. Our bodies are constantly assisted in various aspects by body fluids. Body fluids, in one aspect, serve as a medium for carrying these nutrients to the cells in our bodies as well as moving the waste products from the cells.