Prions have been described for some time in the literature, and certainly are known to the public as Mad Cow Disease. You can read more about prions here.
PDB generated prion image
One of the vexing questions about prions is dose, or more simply is there any threshold amount of material contaminated with prion proteins that might be safe? Prions themselves are very tough and stable proteins. Unlike more other infective material that the public is familiar with, there is no safe way to “cook” meat contaminated with prions that will make it safe for consumption.
With this in mind a research group is looking to see if there is such a threshold dose. Using concepts cribbed from toxicology a lab has looked to see if there is a dose low enough at which prion exposure would not lead to disease. You can read the original paper here, but the take home is that there is no safe dose.
When we were looking through the literature on protein folding diseases, a second paper lept into the light, a recent Tau paper, describing the spread of a misfolded tau protein along the intertwined pathways of neuronal cells. This phenomenon is called “tauopathy”; the progressive spread of misfolded tau protein along specific routes through the brain. This pathology is associated with the development of Alzheimer’s disease. One of the unique findings to this work is the decoding of the spread from one spot to another, involving the jumping of the misfolded protein from neuron to neuron.
Though not yet reproduced this finding holds much promise for future Alzheimer’s disease therapeutics as the protein’s march from cell to cell may provide a weak spot in transmission, allowing us to halt the spread of the misfolded protein, and the progression of the disease.
I am asking the Molecular Toxicogenomics students to write up a post describing how misfolded proteins can be the agents of disease, so if you are interested in the topic, click on through to the comments to get involved in the discussion.
Gillespie Lab 
Proteins can be agents of disease if they become misfolded. For example, degenerative diseases such as Bovine Spongiform Encephalopathy, more popularly known as Mad Cow Disease, is caused by a misfolded protein, generally called a prion. Prions, once in their misfolded conformation, can cause normally folded proteins that surround them to also transform into prions. It has also relatively certain that there is no safe dose of prions. Although probability of infection decreases with a decrease in dose, there is no threshold dose where a specimen will not get sick unless the threshold dose is surpassed.
An example of a misfolded protein is Tau, a protein in the human brain. When this protein is overphosphorylated, it changes its conformation so that it is now a prion and it can not only transform Tau proteins around it to prions but it can also “jump” across neural synapses and spread through the brain. Misfolded Tau proteins are linked to human Alzheimer’s Disease, a degenerative disease of the brain. Prions, therefore, can be very dangerous and infectious.
Your response was very clear and right to the point. I liked how you explained everything in such a way that any random person could understand the ideas you’re trying to convey. Also, i liked how you incorporated information from both of the papers, rather than only concentrating on one over the other.
Maybe focus on one protein and give some examples explaining how this misfolding occurs?
Imagine being in a room surrounded by friends and family having a good time laughing and carrying on and then all of a sudden you don’t know anyone around you think your late for an appointment and you’re in rush but people are holding you back all of a sudden their telling you you’re having an episode. Alzheimer’s disease is one that affects many and has horrible effects that take harmful tolls on a person life endangering them and those around them. It is cause by a misfolded protein that quickly spread throughout the brain infecting cell after cell and causing damage. The research conducted by department of pathology and cell biology at Columbia University on the effect of tauopathy on in both young and adult mice is a start to what can end up to be a miraculous cure with help for many. The effects on the mice prove that the more aged the brain the more susceptible it becomes to AD. The researchers tested on mice young and aged to view the effects the proteins had on the brain with their findings to be that in the aged mice the spreading was to more deeper level than in the young mice. Maybe further studies would be able to determine a cure to this destructive diease.
Prions also know as mad cow disease is a well known name of the last century as it has had a fatal affect on many. The research study conducted by the emerging department of Oxford University shows that even the smallest amount of exposure to prions can be lethal. The study conducted test numerous specimen of prions in different doses and used mathematics to help analyze the results showing that even the smallest amount of exposure proved to be lethal. Meat infected with these prions cause harmful and even fatal effects on the consumer and without a way of killing them off before consumption pose a threat to the consumer. Advancement in the research of folded proteins would lead to cures for both Mad Cow disease and even Alzheimer’s.
I like how specific this person is when talking about the different studies and where they took place. I also thought that it was good to show how a person might be feeling when having this disease because it can put it into perspective. It is tragic that people have to go through this because prions are not curable.
I really like your analogy in the beginning about loss of recognition, “Imagine being in a room surrounded by friends…….then all of a sudden you don’t know anyone around” The saddest and scariest thing is they all recognize you. In a way this is how we are affected by these agents.Our cells are unable to properly use an infected region to its properly. Like if a machine like protien known to spit out spheres (either some ligand, enzyme, nerve impulse, protein, maybe a hormone) to go through a circular path, now if we have ovals not only is this going to not fit properly but this is going to be a cell(the oval) made by the organism and as such its only problem is that it cant do its job. Almost as if to the cell all else had changed. From this there can be several more cascading problems either: the lack of whatever this is supposed to do, our bodies response to a congestion from, needing to cease production, this new chemical triggering a new cell response, now if there is a known way to shut off than hope it is not too late, and how critical completely shutting down certain points would the infected is a region that wont affect mortality. If even possible.
I liked the beginning as well. A careful reading of the Tau paper points out that it is not the age of the mice, but rather in older mice the misfolded protein has had a longer time to spread.
Upon hearing misfolded proteins diseases like Alzheimer’s, Mad Cow Disease, and other Tauopathies come up to mind. All of these diseased listed deteriorate the brain and are caused by an accumulation of misfolded proteins, also called prions. Tangles are formed in by hyper phosphorylation of the tau protein. Through experiments on mice and mathematical calculating, it has been shown that there is no safe dose of prions that will not cause infection. Even with a low dose, the probability of infection is linear to those of the dose amount. Alzheimer’s disease also known as AD is often found in those over 65 years of age. Researchers believe that tangles and plagues in the brain are the cause of this disease and currently without a cure.
Good background on Alzheimer’s disease, allows the reader to understand what the disease is. The experiements on mice indeed show that the tau misfolded protein is what is causing the disease, but there are other factors that can cause the disease. which is why it is so hard to treat and diagnosis.
Excellent focus on the toxicology. Try to focus in on the findings, not just narrative.
Tauopathies are classes of neurodegenerative diseases associated with the pathological aggregation of the tau protein in the human brain. I’m sure you just read that and completely blanked out because it’s another form of English. What I’m trying to say is that tauopathies are a class of diseases that affect the human brain. They are associated with the buildup of the tau protein. I hope that clarified everything. The misfolding of proteins is associated with neurodegenerative diseases such as mad cow disease and Alzheimer’s disease. The earliest stages of Alzheimer’s disease show accumulation of the misfolded tau protein in the entorhinal cortex and the hippocampus. Both of these regions in the brain work in the memory system. Therefore, the tau protein is clearly responsible for the symptoms associated with Alzheimer’s.
Prions are infectious disease causing agents that are composed of misfolded proteins. Prion diseases or transmissible spongiform encephalopathies (TSEs) are also involved in neurodegenerative diseases such as the mad cow disease. There are two different types of prion proteins, a normal form and a misfolded form. The misfolded form has the ability to force the normal prion proteins into becoming misfolded prions. Misfolded prion proteins are so fatal that even the smallest dosage can infect entire organisms, causing neurotoxicity. Therefore, we can conclude that there are no safe doses of prions that are safe for any individual, man or animal.
I agree that its another form of English which made it a little harder to read I had to read it twice and highlight. I like how you went from alzhimers disease and then linked it to prions. Overall I think it is a good response.
It is another form of english, but a useful one. Be careful though, it can sound as if you are belittling the reader with phrases like “I’m sure you just read that and completely blanked”. Instead, draw the reader in with an example.
I am really pleased with your informative description of Prions, and how these infectious disease causing agents are associated with neurodegenerative diseases such as Alzheimer’s disease. Furthermore, you provided an evident explanation that “accumulations of the misfolded tau proteins in the entorhinal cortex and the hippocampus” are associated with symptoms of Alzheimer’s disease, since these regions in the brain are vital for memory.
Prions are characterized as a misfolded protein state. Alzheimer’s disease is caused by protein misfoldings.Alzheimer’s disease occurs when there is an accumulation of plaques called the beta- amyloid. These plaques are formed from the misfolding of proteins or prions. When the protein forms incorrectly , it binds to other protein’s hydrophobic region. Then it forms the plaques that are found in Alzheimer patients. Another disease that is caused by the misfolding of proteins is cancer. The p53 protein is altered which causes the mutation. A mutation that occurs in the p53 protein is likely to occur in 50 percent of all cancers. The p53 protein can be activated because of stress or by a disruption in the DNA strand. After the p53 protein is activated, it migrates to the cell nucleus and activates other proteins. This leads to cell proliferation and apoptosis. Protein misfoldings can cause many diseases that are threatening to the human body.
Mishkat, what you have so far is very informative and true. I like how you included a disease caused by protein misfolding that we talked about in class, but you may also want to include information about mad cow disease to include the other article as well. Otherwise your response was very informative.
Usually protein folding is carried out successfully by the body, but sometimes protein misfolding results. Usually this happens to one of the proteins and that protein is usually nonfunctional and does not harm or alter the transformation of the other proteins around the misfolded one. However, this is not the case with prions, which are proteins that have been misfolded, but are able to do something very special. This misfolded protein is not simply a misfolded protein, because it has the ability to make normal proteins around it misfold as well suggesting that misfolded proteins are an agent of disease. The disease that prions cause is bovine spongiform encephalopathy, which is better known as Mad Cow Disease by many people. By forcing the other proteins around the misfolded protein to change their shape to a misfolded one, soon most proteins around the original misfolded prion are misfolded and are unable to perform the function that they were supposed to perform. Even one misfolded prion has the ability to change many other proteins’ shapes, which is why no dose of prions is safe. This is verified by the article by Helen R.Fryer and Angela R. McLean called “There Is No Safe Dose of Prions”. In the article, these scientists test doses on rats from high doses to the most dilute doses, which were diluted ten-fold. Yet even the most dilute doses of prions exposed to a mouse resulted in the infection of the mouse within a matter of days.
Yet, this is not the only example of how a misfolded protein was the agent of disease. This is also seen by the tau protein which spreads synoptically through the nerves in the brain causing Alzheimer’s in elderly people after it spreads widely. In the article, “Trans-Synaptic Spread Of Tau Pathology In Vivo”, the spread of the disease is seen through figure one , where it shows that the misfolded protein started out in the entorhinal cortex and then spreads to other parts of the brain from there synoptically spreading the misfolding similar to how the prions do in the bovine spongiform encephalopathy. However the difference is that the tau protein was able to travel through nerve impulses to other parts of the brain and then spread the misfolding, while the prions were able to force other proteins to misfold if they were in the immediate vicinity. Proteins when misfolded are the agents of disease, which is exemplified through the two diseases bovine spongiform encephalopathy. Although the spread of the disease is different, they both start with one misfolded protein that then infects the other proteins in the other parts of the brain.
Your response to this topic reflected your understanding but, what do you think about the evidence found. The foundation to the argument is how the misfolding of proteins cause this effect. I think you show good knowledge but, I think the research itself can only prove how is it effects mices and the particular age group. I definitely agree with that prions have a deeper characteristic than just effecting other proteins.
Great data write-up, but give the reader as description of the figures that you are citing, so they can follow along as well.
Misfolded proteins are often found to be the cause of diseases. An example of this includes transmissible spongiform encephalopathies (TSEs), or prions, which are misfolded proteins that cause diseases such as mad cow disease and Alzheimers. It has been proven that there is no safe amount of prions if they are taken into the body. Prions are able to cause the normal proteins around them to also misfold. Usually, the misfolding of these proteins will cause brain damage. For example, mad cow disease (Bovine Spongiform Encephalopathy) is when the brain will start to deteriorate. A symptom of this disease is when the brain accumulates the abnormal proteins. Most of the time doctors will not notice this until after death and they examine the person’s brain.
I agree with you that most patients with AD will not be found out until the last stage or even their death. I’d also like to point out that the same thing happens with mad cow disease. Even though a cow can be obviously very sick, it is still hard to determine what the real infectious agent is. Imagine when a protein sees other protein which may appear to be its own kind that is correctly folded, however, when it binds to that protein, it turns out to be folded in a wrong way. And as this property expands, the illness grows worse in one’s body.
As many people may still wonder about what the real cause of Alzheimer’s disease is, a recent study in mice shows that tauopathy, a type of the neurodegenerative diseases caused by the deposition of tau within the brain, can be a very crucial signal of AD. On the other hand, patients with AD are usually found out they have amyloids folded abnormally which contain plaques in their brains. And this new discovery can be related to some other disease, such as Mad Cow disease as it is thought to be caused by a misfolded protein, prion, which can even cause other proteins misfolded.
Moreover, both tau and prions are very difficult to detect. Although a cow may appears to be very ill, there is few infectious agents can be recognized as prions. Same with AD, even though the trans-synaptic spread of tau pathology is identified in the entorhinal cortex, the mechanism still remains unknown. Surprisingly, there are still so many scientists and doctors working on AD and Mad Cow disease as the fact they are totally fascinated by the “trouble makers”, such as tau and prions.
I feel that your response is well written in that it is short yet at the same time provides details and description toward the underlying threat that the two articles examine. Also the way you describe how tau and prions are hard to detect emphasizes the danger of diseases cause by misfolded protiens.
Make sure to keep separate topics separate. Both are related to misfolded proteins, but the routes the diseases take and the reasons that the proteins are misfolded are different.
Bovine Spongiform Encephalopathy (BSE), or mad cow disease is thought to be caused by a “prion”. This protein acts as a template to cause proteins in the brain to mis-fold into shapes in which they do not serve their intended purpose. It also can not be fixed by the body’s repair mechanisms. The concept of a prion is known as an improperly folded protein which transform normal proteins to take this course and alter their characteristics. This leads to widespread damage to the brain. To demonstrate this is in fact disease causing, research by Oxford University emphasize how lethal prions at any dose can be. Data analyzed from 4,338 mice assess the risk from low dose exposure and compared to results from a within-host model in which prion accumulate according to stochastic birth-death process (Fryer et al.). The mice showed a host of symptoms of TSEs after injection. Brain tissues from diseased mice were then injected into the brains of a group of additional mice to test for transmission of the illness. These mice also developed prion disease. It is proposed how the prions are propagated to cause the detrimental damage. The study effectively concluded the probability of infection to decrease as the dose decreases thus, threshold dose can no be established. Therefore this exposure is lethal. The misfolded Tau protein found in the human brain tends to change conformation to become prion-like in its functionality and characteristic. The conjugated Tau protein may be even mordant. Tauopathy is actually found in the brain of patients with Alzheimer’s disease and starts in the entorhineal cortex and spreads throughout synaptically. Research conducted at Columbia University widely illustrates the effect of taupathy in mice, distinguishing the effects in both young and adult mice. Respectively, the younger mice showed signs of more superficial tissue damage as the elderly mice showed more intrusive damage into deeper layers of tissue which correlates to the extent of Alzheimer’s symptoms associated. This neurodegenerative disease is again linked to the misfolding of proteins. This proves further research must be done to fully elaborate on the mechanism and effects misfolded proteins induce. These studies prove misfolded proteins are in fact the underline cause and it is in fact life-threatening since minute amounts can quickly spread and infiltrate the tissue of the brain.
I really liked the depth of this write-up. Nice job.
Great analysis of what exactly happened in the procedure to the subjects. Excellent vocabulary use, too. The only sentence I felt was where the older mice and younger mice were being compared? Perhaps I misread, doesn’t the younger mice show that they too have intrusive damage as you referred to it?
Anyone with an understanding of Biology will agree that proteins control a lot of what goes on inside our bodies. They work as antibodies against foreign particles, carry out chemical reactions as enzymes, transport materials, and more. So it’s easy to see that proteins are definitely essential to our well-being. Proteins are known to “fold” into various shapes depending on their assigned task. Each particular shape, down to the last detail, is important for that protein to function properly. But what if these proteins were to malfunction? The most common way proteins tend to breakdown is by misfolding. Once this happens the protein stops working completely thus causing complications to a persons health. Recent studies show that Alzheimer’s disease is a product of this phenomenon. A misfolded protein causes plaque build up inside a part of the brain. Then this protein travels to other parts of the brain generating more plaque which eventually leads to Alzheimer’s disease. This also appears to occur inside animals such as cows. Prions are the result of misfolded proteins inside a cow leading to the infamous Mad Cow Disease. Hence, the folding of proteins is vital to good health.
Your response was really good. It is short and to the point. I like how you gave background information on proteins so anyone can understand the concept of prions. I think you should add some evidence from research to further support your response.
Prions are a complex protein that can cause disease in the public. It has been proven by scientists that there is not safe dose of prions that even the slightest amount can cause pathological effects. Prions are quite durable and hard to break down which makes them very dangerous. Prions are basically misfolded proteins and have shown to cause Mad Cow Disease. One prion that has shown to cause Alzheimer’s is Tau, which have been found in patient’s brain biopsies. The neurons relay the misfolded protein and infect other neurons which spread the disease. There are other theories for what causes Alzheimer’s which is what it is so hard to find a treatment. In the end the struggle is to figure out how to break down the prions so that they can be treated.
There are two main causes of Alzheimer’s disease that scientist have been looking at are plaques and tangles, and in this article we look at tangles. that deposits of the protein tau and accumulate inside of nerve cells.
And also even one misfolded protein can change many other protein’s shape and cause disease to happen. and the disease is called bovine spongiform encephalopathy that’s why there is no safe dose of prions.
Proteins are perhaps the most important substances in most fields of biology at one point even being considered to serve a similar to genetic data by scientists. While we now know that isn’t true we still continuously studied proteins to further our knowledge of the way different proteins work and form. These papers are quite interesting because of their discussion of protein malfunction and the relation of this to Alzheimer’s disease. While one paper disscusses the danger of prion concentration and the uncertainty of whether a prion will prove harmful or not, the other paper maps the pathway of Alzheimer’s disease and describes the Tau Proteins involvement in this process. As we continue to observe and experiment with prions and Tau proteins it may be possible to produce or isolate (from nature) a possible solution to the prion problem. While these papers only suggest and describe mechanisms of prion growth and Alzheimer’s pathway this information should be considered vital and used in follow up experriments. Metaphorically speaking now we understand how the enemy works, so what we must look for is something that will interfere with their process.
Furthermore to specifically address the danger of Alzheimers we must understand the function of proteins in the body. The body store a plethora of proteins each with own said purpose which altogether provide the body with important life functions at a cellular level. The protein relies on its structuce to perform its tasks, this structure is based of the proteins primary amino acid sequence. Alteration of the primary sequence would mean a complete change in function. This is why alzheimer’s disease is dangerous because of the alteration in protein function to cause the protein to harm its own body/cell. But the reason why Alzheimer’s is such a great threat is that not only does the protein become harmful to its own cells and body but it behaves like a virus (called prion) it somehow manages to alter other proteins that are the same and turn them into prions as well. As one of the paper adequately shows prion growth is not easy to predict depending on the spread of the prions, the disease may or may not actually come to pass. This is one of the mysteries remaining regarding Alzheimer’s because of the unpredictability of prion population growth.
Very good response. I liked how you showed the true importance of proteins in the human body and the danger of misfolded proteins, which can cause much harm and can be very infectious. The inherent danger that prions pose to health is very clear given your response.
The misfolded proteins often cause some of the diseases, an example of it is the transmissible spongiform encephalopathies (TSEs) or called prions, these cause Alzheimers or mad cow disease. The protein acts as a template and that causes the proteins in the brain to be mis-folded into shapes that even the body repair mechanism cannot fix. Prion is considered to be an improperly folded protein and causes those proteins to change their function causing widespread damage to the brain. The misfolded protein has the ability to make normal proteins to cause disease. The disease that prions cause is bovine spongiform encephalopathy. The data shown in the article provides us with details that there is no dose of prions is safe since even one misfolded prion can change many other protein’s shape. The experiment was done with mice with the prion dose of high and from the lowest diluted prion dose. The mice had host of symptoms of TSEs after injection. They also did the study of transformation of the disease by inserting the brain tissue of the diseased mice into the no diseased mice and they found out that even those mice developed the prion disease.
The example of misfolded protein is Tau that is a protein in human brain. When the protein gets overphosphorylated the conformation changes and becomes prion so that it can’t transform Tau proteins around it to prion but also go across neural synapses and spread throughout the brain. The Tau proteins are correlated to human Alzheimer’s Disease. The research done proves that misfolded proteins are very dangerous and infectious.
Please be careful not to mash-up the two diseases. They are quitte different (see previous comments to the same).
Your last paragraph is right on track and I would love to see that sort of writing expanded.
I believe the addition of the tau paper was helpful to aid as a bridge between an experiment done at the prime of neural sciences compared to a more modern look at the neural-biological pathways as lines out. My only concern is how this shatters the myth behind us only using ten percent of our brains. Every disease either starts from a misunderstood or lack of call signaling. This originates as the cell folds as it situates what will be on and have access to its extremities. I know this sounds quite silly but in a way i really fear these prions due to their tendency to contain the basic instinctual need of increasing ones kind. On a petri dish millions of thousands of cells like how millions of people cover the earth. A virus would replicate and lyse a cell this however seems have patience. As if learning what we are capable of. It is a conspiracy in the microverse. Who knows maybe one day prions may become our medicines. In an evolutionary stand point to admit perfection is giving-up (bio-chemists may agree) These abnormalities have a way of changing parts of us. Not all change is bad. If we can find a prion that can target a virus than maybe we can let our immune system hire out freelance for a change. Sadly when i Googled prion and virus in the same sentence i got several results on the possible impending Zombie Apocalypse. Good luck everyone
You start with some good ideas that hook the reader, but quickly degrade into a jumbled narrative. I know that you can do better.
I like your idea of prions actually become a medicine. It it does all the better for us. Virus adapt just like how we have to adapt to survive. Its just like in our experiment last week where some bacteria had the GFP gene and were able to have resistance against ampicillan.
Many scientists have turned to misfolded proteins, or prions, to be agents in disease. Bovine Spongiform Encephalopathy (BSE), or mad cow disease, is caused by a prion. In mad cow disease patient’s, the brain accumulate the abnormal proteins. Doctors don’t detect this until after they examine the person’s brain after death. An example of a prion is a misfolded version of Tau, a protein in the human brain. When this protein is over-phosphorylated, Tau changes confirmation, and becomes a prion. These misfolded Tau protein can transform normal Tau proteins around it into the prion. It can also “jump” across neural synapses and spread through the brain. These misfolded Tau proteins has been linked to Alzheimer’s disease, a degenerative disease of the brain. The earliest stages of Alzheimer’s disease show accumulation of misfolded tau protein in the entorhinal cortex and the hippocampus. Both brain regions are involved with our memory. Research done on prions proves that they can be dangerous and infectious. As we continue to observe and experiment with prions, it may be possible to find a solution to this prion problem.
Be careful, Tau is not a prion.
Overall I think this a very good response. I think you did a good job in the way you explained how the Tau protein works. I also liked that you linked the fact that because tau accumulates in the enthorhinal cortex and hippocampus, which controls memory it leads to Alzhemier’s disease. In addition, further explaining how prions function would strengthen this piece.
Proper protein folding is essential to the biological processes that carry out life. Prions are proteins that have two forms, a normal and a misfolded form. The misfolded prion can force normal prions to conform to the misfolded shape. In its normal form the prion protein PrP is found on the surface of nerve cells. However, when it changes into its misfolded form it clogs the normal functioning of the brain by aggregating into long fibrils. The misfolding of the PrP prion causes fatal neural diseases in human and other mammals. Some examples include Bovine Spongiform Encephalopathy (mad cow disease) in cattle and Creutzfeldt-Jacob disease in humans (human version of mad cow disease). Prion infection occurs when a little bit of the misfolded protein is eaten or accidently enters the bloodstream through injury. Prions are very infectious and a small dose can infect the entire organism. As the misfolded proteins build up there can be deadly consequences. There has been research done to prove with relative certainty that there is no safe dose of prions, although a decrease in dose does decrease the probability of infection.
Tau proteins are proteins found in the brain that stabilize microtubules. “Tauopathy” is the spreading along specific routes of the brain of the misfolded tau protein. When a tau protein becomes hyperphosphorylated it is transformed into a prion. It can now transform other tau proteins into prions and “jump” across neural synapses allowing it spread to other parts of the brain. The hyperphosphorylation of tau proteins cause them to become defective and no longer stabilize microtubules properly. This can lead to degenerative diseases of the brain such as Alzheimer’s disease.
Prions are very infectious agents that can have disastrous results on the organism they infect. They slowly kill off the organism by causing degeneration of the nervous system and can not be fought off by the immune system since they are recognized as “self.” Hopefully with continued research a solution will be found to prevent misfolding proteins from conforming other normal proteins, thus solving prion related diseases.
Your response was very informative. Describing how Mad Cow disease and Alzheimer’s disease is created. Also, going in-depth as to how Alzheimer’s disease is spread. However, I wish your response flowed a bit better; it feels choppy at certain spots.
Proteins are probably the most important class of biochemical molecules, having many diverse functions that are essential for life. Proteins are the basis for the major structural components of animal and human tissues. To form a protein, one or more polypeptide chains are twisted into a 3-D shape. This unique shape of the protein is what determines its function. However, sometimes proteins become misfolded, and these misfolded proteins turn into the abnormal, pathogenic agents, better known as Prions. These disease causing agents, are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain.
The outcome of the misfolded proteins poses a risk to public health. Prions are well-known to us with an association of Mad Cow Disease. Another one of the most devastating diseases caused by misfolded proteins is Alzheimer’s disease. Research indicates that the underlying causes of Alzheimer’s disease are the abnormal build-up of beta – amyloid peptides in the brain. These abnormal accumulations of misfolded proteins form plaques in the brain, which ultimately impair memory by disrupting memory-related functions of synaptic junctions between neurons. Once a misfolded protein, a prion, enters a human brain, it causes the healthy, normally folded proteins to change into the disease causing form. Prions also have the ability to act as a template, directing the misfolding of more proteins into prion forms. This process of converting more proteins into a misfolded form generates a chain reaction that leads to a production of large quantities of prions.
Consequently, such abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease. Unfortunately, Prion diseases are usually rapidly progressive and always fatal, even at extremely small amount of exposure.
I like that you talked about Alzheiemer’s disease and its connection to prions. You were able to use scientific term such as beta-amyloid peptides and explain their functions so that any one could read your response and understand what you were talking about. Your response was longer than most, however you went in depth to describe how a prion is formed and how it effects the brain, which is important.
A misfolded protein in an infectious form, is referred to as a prion. Once a prion is formed it starts a chain reaction within your proteins, misfolding a large amount of proteins. A prion will disrupt the neural tissue, which makes up the brain, and eventually promote cell death. It does this by creating Amyloid (a plaque) which disrupts your normal tissue growth. Prions are resistant to forms of denatration, which makes it almost impossible to get rid of them. This is why most prion diseases eventually lead to death. Proteases is the enzyme in our bodies which breaks up proteins. PrP is the protein which can lead to Prion production, if found in infectious material it is resistant to proteases. Prion disease includes BSE, Scrappy, and CJD. These diseases lead to neurodegeneration, usually resulting in death.
Why does the plaque cause cell death? I’m sure there’s a good answer to this, but I didn’t quite get a good understanding about that from the paper. Also, it is interesting that protease does not denature prions. I think this is because prions are misfolded in a way that the hydrophobic portion of the protein chain is exposed, making hydrolisis of the protein impossible. Is that what happens or did that only sound good in my head?
For starters the paper was set up really well where I felt I understood it at best.
The most effective part was: Prions and their exposure can lead to TSE’s such as Mad Cow Disease or Tau-related Alzheimers. TSE’s spread has all begun, according to this study and analysis, from polymers. For example, the PrP^Sc form of PrP^c occurs only when in the presence of polymers which have a certain length that can cause such misfolding. That being one key factor, length, another is rapid replication of the misfolded proteins. When taking place both of these cause and effects can propagate an infection where the prions could get to elsewhere in the organism.
The thesis: Focusing on the three questions proposed earlier in the paper, the central message was that if prions are tested and show no harmful effects immediately, still there can be no such a “safe dosage” of prions no matter how miniscule.
Each of the question was answered in full and were thoroughly explained: First off the threshold dose isn’t a certainty rather a recorded test that there’s no safe dose even at the smallest levels seen. There’s a threshold, yes, but of the general harmfulness that shouldn’t be crossed (paraphrased from data and review on Pg. 2,4-5 All left side columns). Second, The results discussed later in detail were able to answer the remaining two questions which ask about the correlation between dosage and incubation period over time. As noted, results showed to be Stochastic, for better words, inherently random, because the dose’s relationship with the incubation periods being inversely squared (observed on pages 5 and 6 graphs).
Overall, there was no significant portion that wasn’t effective or out of order at all. The statements were complete and concise. The results were explicit, even providing mathematical data to further support answers to the thesis and questions. This paper served as an established outline in order to better attempt the the ‘Tau’ paper.
Tau Pathology Paper
Trans synaptic Spread in Mice:
The explanation as to what exactly Alzheimer’s is according to biological terms was a necessary and intriguing addition. The diagram offered me as the reader a mini mapping of how the synaptic processes flow through the main cortices. This was a terrific starter and most effective piece for the experiment.
The least effective with the study was the antibody CP-27 compared to MC1? Why using this one, too? I was a little confused with the Silver staining and how the methods and the tools that are used for the procedures were placed at the end more descriptively. There should be more of a flow between this and where exactly the discussion of results are written in the paper.
Thesis is that the Tau can spread throughout an organism, destroy cells, and essentially cause Alzheimer’s, or impede the cell growth.
The results and discussion on (Pg. 3&4) were heavily supported with the figures 2 and 3 that were stated. The information of figure 8 on page 7 is right on the spot, corresponds fully with the hypothesis. The photographs showed some unclarity when referring back to the CP-27 because the MC1 should be used twice no? The non Tg mouse versus the Tg mouse should both be studied with the same MC1, no?
Correct folding of proteins is vital to their proper functioning. An error in conformation can lead to disease, and this is often the culprit behind degenerative diseases. When a protein is denatured, its primary bonds, that hold the structure together, are disrupted and the protein begins to unfold. Proteins can fold back together, but if they follow the wrong pathway and do not fold back in a way that create energy-minimizing bonds, the proteins misfold. Proteins are usually produced correctly in the body, but sometimes they sporadically arrange into a toxic form, known as a prion.
The most common prion-caused degenerative disease is Alzheimer’s, which can be sporadic or familial. As we age, protein folding becomes less accurate, leaving us more susceptible to misfolding. Misfolded proteins aggregate and form a plaque in the brain. Properly folded proteins fold in a way so that the hydrophobic portion of the chain is away from water. It is believed that the misfolded proteins that cause Alzheimer’s fold incorrectly, leaving the hydrophobic portions exposed, wanting to bind to something that will protect them from water, leading to plaque buildup.