Prions - Online Tutor, Practice Problems & Exam Prep

Prions are misfolded proteins that act as infectious agents, leading to neurodegenerative diseases like Creutzfeldt-Jakob disease and scrapie. The normal prion protein (PrPC) can be converted into the disease-causing form (PrPSc) through interactions, resulting in the accumulation of PrPSc in neural tissue. This accumulation causes spongiform encephalopathies, characterized by sponge-like lesions in the brain. Understanding prion development is crucial for grasping the mechanisms behind these debilitating diseases and their impact on both human and animal health.

Prions

This video we're going to begin our lesson on prions. First, we need to recall from some of our previous lesson videos that the term prions is derived from proteinaceous infectious agents. You can see the "p r," the "I n," and those are also found here in prions. These prions, or proteinaceous infectious agents, like viruses and viroids, are also acellular obligate intracellular parasites. However, unlike viruses, which are made of proteins, nucleic acids, and sometimes lipids, and viroids, which are only made of RNA, prions, as their name implies with the proteinaceous part, are only made of misfolded proteins. Now, these prions can cause normal proteins to misfold, which can ultimately lead to some type of neurodegenerative disease.

Notice down below over here on the left-hand side of our image, we're showing you some prion diseases or diseases caused by prions in humans, such as Creutzfeldt-Jakob disease, familial fatal insomnia, and kuru, and then also some prion diseases that cause disease in animals such as scrapie, mad cow syndrome, and chronic wasting disease. These prions can ultimately accumulate in neural tissue such as, for example, the brain, and they can cause what are known as transmissible spongiform encephalopathies. These transmissible spongiform encephalopathies are when brain tissue deteriorates, forming holes and a sponge-like appearance in the brain.

If we take a look at our image down below, notice on the left-hand side over here, what we're showing you is a micrograph of a normal brain, of normal brain cells. On the right over here, what we're showing you is a brain with spongiform encephalopathies. What you'll notice is that the brain with spongiform encephalopathies has these spongiform lesions, basically these holes, and it is deteriorating. All of these holes, these gaps that you see here, this is what gives the brain a sponge-like appearance, which is where it gets its name, spongiform encephalopathies.

Ultimately, again, these are going to be associated with prion formation and can lead to these degenerative diseases that we have here. This here concludes our brief introduction to prions, and we'll be able to talk a little bit more about prions as we move forward in our course. I'll see you all in our next video.

Prion Development in Neurons Leads to Scrapie

This video, we're going to be talking about prion development in neurons leading to the disease scrapie in animals. And so the infectious prion protein that is misfolded leading to the disease scrapie is PrP_Sc, which is really just an abbreviation for prion protein scrapie. And the normal form of that prion is actually PrP_C, which is prion protein cellular, and so PrP_C is the normal protein with normal function, and PrP_Sc is the prion that leads to the disease scrapie. And so the accumulation of PrP_Sc, the prion form, in the brain is attributed to its interaction with the normal protein, which is once again PrP_C.

And so the interaction between PrP_Sc, the prion, and the normal protein, PrP_C, is going to cause the normal protein, PrP_C, to misfold. And if the PrP_C protein misfolds, it is going to result in a PrP_Sc prion. And so the PrP_Sc prion will accumulate over time through interacting with PrP_C and converting the PrP_C to PrP_Sc. And so, PrP_Sc accumulates and begins to aggregate in the brain leading to spongiform encephalitis and the disease scrapie in animals.

And so if we take a look at our image down below we can get a better understanding of the prion development in neuron cells and how that results in the neurological disease scrapie in animals. And so notice on the far left over here we're taking a look inside of a neuron which is a type of cell of the nervous system. A cell that can be found in the brain. And so inside the neuron there, can be, PrP_C, which is the normal functioning protein with the correct shape, but if there is a prion, it will be PrP_Sc. And so if they're both present in, a neuron cell, what can happen is the PrP_Sc can interact with the PrP_C.

And so the misfolded PrP_Sc prion protein can interact with the normal PrP_C protein. And so the misfolded PrP_Sc prion can convert the normal PrP_C into PrP_Sc. And so notice that the PrP_Sc is accumulating, and so it can continue to interact with other normal PrP_C proteins and the continued conversion as PrP_CPrP_Sc accumulates. And so the accumulation of PrP_Sc is going to lead to the aggregation of PrP_Sc aggregation, and ultimately that clumping can lead to causing spongiform lesions which are those holes that you can find in brain tissue, and that leads to the disease scrapie in animals.

And so really these prions once again are just misfolded proteins that can interact with normal proteins and cause the normal proteins to also misfold and become prions. And so this here concludes our brief lesson on prion development in neurons leading to the disease scrapie, and we'll be able to get some practice applying these concepts as we move forward in our course and so I'll see you all in our next video.

Here’s what students ask on this topic:

What are prions and how do they cause disease?

Prions are misfolded proteins that act as infectious agents, leading to neurodegenerative diseases. Unlike viruses and bacteria, prions lack nucleic acids and are composed solely of protein. The normal prion protein (PrPC) can be converted into the disease-causing form (PrPSc) through interactions with misfolded prions. This conversion results in the accumulation of PrPSc in neural tissue, causing spongiform encephalopathies. These are characterized by sponge-like lesions in the brain, leading to diseases such as Creutzfeldt-Jakob disease in humans and scrapie in animals. The accumulation of PrPSc disrupts normal cellular functions, ultimately causing cell death and tissue damage.

What are some examples of prion diseases in humans and animals?

Prion diseases, also known as transmissible spongiform encephalopathies, affect both humans and animals. In humans, examples include Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, and kuru. In animals, prion diseases include scrapie in sheep, mad cow disease (bovine spongiform encephalopathy) in cattle, and chronic wasting disease in deer and elk. These diseases are characterized by the accumulation of misfolded prion proteins in the brain, leading to neurodegeneration and the formation of sponge-like lesions in neural tissue.

How do prions differ from viruses and viroids?

Prions differ from viruses and viroids in their composition and mechanism of infection. Prions are composed solely of misfolded proteins, lacking any nucleic acids. In contrast, viruses contain proteins, nucleic acids (DNA or RNA), and sometimes lipids. Viroids are simpler than viruses, consisting only of a short strand of RNA without a protein coat. While viruses and viroids rely on their genetic material to replicate and cause infection, prions propagate by inducing normal proteins to misfold, leading to the accumulation of pathogenic prion proteins and subsequent neurodegenerative diseases.

What is the mechanism behind prion-induced neurodegeneration?

Prion-induced neurodegeneration occurs through the conversion of normal prion proteins (PrPC) into the misfolded, disease-causing form (PrPSc). This conversion is initiated by the interaction between PrPSc and PrPC. The misfolded PrPSc induces the normal PrPC to adopt the abnormal conformation, leading to the accumulation of PrPSc in neural tissue. Over time, these misfolded proteins aggregate, forming clumps that disrupt cellular functions. The accumulation of PrPSc causes spongiform lesions, characterized by holes in the brain tissue, which impair neural function and lead to cell death, resulting in neurodegenerative diseases.

What are spongiform encephalopathies and how are they related to prions?

Spongiform encephalopathies are a group of neurodegenerative diseases characterized by sponge-like lesions in the brain. These lesions are caused by the accumulation of misfolded prion proteins (PrPSc) in neural tissue. The normal prion protein (PrPC) is converted into the disease-causing form (PrPSc) through interactions with existing misfolded prions. This conversion leads to the aggregation of PrPSc, forming clumps that disrupt normal cellular functions. The resulting tissue damage and cell death create the characteristic sponge-like appearance in the brain, leading to diseases such as Creutzfeldt-Jakob disease in humans and scrapie in animals.