prion proteins

Cannibalism can be very dangerous to the body. You open yourself up to more diseases eating human flesh. Viruses tend to be very specific to a species, and it is rare for them to jump. So if you are eating beef meat contaminated with some virus that is affecting the cow, chances are you won’t catch it. But if you are eating human flesh, that is contaminated with HIV, you now have a very good chance of contracting it. Kuru is a disease that spreads almost exclusively by cannibalism. It is a mutated prion (protein) that can spread to surrounding brain matter. Resulting in a loss of motor control, impaired cognitive abilities, uncontrolled laughing, swelling in joints, and eventually death. (Source)

Prion-like protein spotted in bacteria for the first time

Prions, the infectious agents best known for causing degenerative brain disorders such as ‘mad cow’ disease, may have been spotted in bacteria.

A section of a protein in Clostridium botulinum, the microbe that causes botulism, can behave like a prion when it is inserted into yeast and Escherichia coli bacteria, researchers report in the 13 January issue of Science1.

Prions are formed by proteins that can fold in a number of structurally distinct ways. A prion version of a protein can perpetuate itself in an infectious manner by converting normal forms of that protein into the prion version.

Scientists first discovered prions in the 1980s as the agents behind fatal brain disorders known as transmissible spongiform encephalopathies. Since then, researchers have found the misfolded proteins in mammals, insects, worms, plants and fungi2, and learned that not all prions harm their hosts.

But until now, prions were only seen in the cells of eukaryotic organisms, a group that includes animals, plants and fungi.

Clostridium botulinum harbours a protein that acts like a prion in other bacteria. James Cavallini/SPL

Plant protein behaves like a prion

Prions, the misfolded proteins that are known for causing degenerative illnesses in animals and humans, may have been spotted for the first time in plants.

Researchers led by Susan Lindquist, a biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, report that they have found a section of protein in thale cress (Arabidopsis) that behaves like a prion when it is inserted into yeast.

In plants, the protein is called Luminidependens (LD), and it is normally involved in responding to daylight and controlling flowering time. When a part of the LD gene is inserted into yeast, it produces a protein that does not fold up normally, and which spreads this misfolded state to proteins around it in a domino effect that causes aggregates or clumps. Later generations of yeast cells inherit the effect: their versions of the protein also misfold.

This does not mean that plants definitely have prion-like proteins, adds Lindquist — but she thinks that it is likely. “I’d be surprised if they weren’t there,” she says. To prove it, researchers would need to grind up a plant and see whether they could find a protein such as LD in several different folded states, as well as show that any potential prion caused a misfolding cascade when added to a test-tube of protein. Lindquist adds that because she’s not a plant scientist — her focus is on using yeast to investigate prions — she hasn’t tried these experiments. The study is reported on 25 April in the Proceedings of the National Academy of Sciences1.

A protein in thale cress (Arabidopsis, pictured) behaves like a prion when it is expressed in yeast. Kristopher Grunert/Corbis/VCG

OB Science Time: The Castor Disease

Episode 3x03 had a lot of science in it, so it’s time for a second edition of OB Science Time to discuss the science behind the Castor Disease, or “glitching”.

Scott says, upon examining Seth’s brain that “it looks like Swiss cheese” and he mentions encephalopathy as well as Creutzfeldt-Jakob disease. Encephalopathy is an umbrella of diseases categorized by an altered mental state, including symptoms such as loss of cognitive function, subtle personality changes, and inability to concentrate. We certainly saw these symptoms in Seth, with his inability to perform well on Paul’s syllogism test, as well as his violent outburts and his mutterings in the stairwell before his final episode.

Creutzfeldt-Jakob disease is caused by prions, which are misfolded proteins that then act as an agent to convert their properly folded counterparts into more prions. The classic result of these prions is a change in the gray matter of the brain, causing large vacuoles to form, giving the appearance of Swiss Cheese. Symptoms of this disease include memory loss, personality change, and hallucinations, as well as jerky movements and seizures.

My guess is that the Castor disease functions in a similar manner as these diseases. Scott also mentioned the presence of amyloid plaques in Seth’s brain, which are protein aggregates. These aggregates, which could be made up of prions, could be causing neurodegeneration, leading to the Castor glitches and altered mental states.

It will be interesting to see what Cosima and Scott do with this knowledge, and more importantly, how the Castor clones will go about finding a cure for their malfunction.

My ask is always open for any questions or comments, and you can find more OB Science Time here!! :D

OB Science Time: The Clone Disease

What an episode that was! After all the information we learned in 3x06, I have decided to devote an OB Science Time to discussing the clone disease.

The most exciting revelation for me was that the Castor and Leda diseases are really one and the same. The disease is caused by a misfolded protein, which can be referred to as a prion. The protein misfolds and disrupts function, and then causes tissue degradation. In the case of the Castor clones, the brain degrades, while in the case of the Leda clones, the endothelial tissue degrades, beginning with the uterus and then spreading to the lungs and other organs.

Unfortunately, the Castor clones can also transmit this disease sexually, as well as via blood. The women in the notebooks that the Castor clones slept with all ended up with the prions in their blood, and degradation of the ovaries leading to sterilization. Dr. Coady had plans to harness this sterilization ability and use it as a weapon to essentially wipe out enemies via sterilization.

Sarah, and of course Helena, are unique in that they are Leda clones that should have the defect, yet they are fertile. It appears that something in their DNA prevents the prion from attacking their bodies. This may mean that the twins could be useful in developing a cure, as their genetics may hold a sequence that could be used for gene therapy, or something about their biology could lead to a cure.

I’m excited to see where the show will go from here, now that Coady’s work has been blown up and Sarah and Helena have escaped. My ask is open for all discussions and questions :D

nature.com
Genetic mutation blocks prion disease
Unknown mechanism helped some people in Papua New Guinea escape historic, deadly outbreak.

Scientists who study a rare brain disease that once devastated entire communities in Papua New Guinea have described a genetic variant that appears to stop misfolded proteins known as prions from propagating in the brain1.

Kuru was first observed in the mid-twentieth century among the Fore people of Papua New Guinea. At its peak in the late 1950s, the disease killed up to 2% of the group’s population each year. Scientists later traced the illness to ritual cannibalism2, in which tribe members ate the brains and nervous systems of their dead. The outbreak probably began when a Fore person consumed body parts from someone who had sporadic Creutzfeldt-Jakob disease (CJD), a prion disease that spontaneously strikes about one person in a million each year.

Scientists have noted previously that some people seem less susceptible to prion diseases if they have an amino-acid substitution in a particular region of the prion protein — codon 1293. And in 2009, a team led by John Collinge — a prion researcher at University College London who is also the lead author of the most recent analysis — found another protective mutation among the Fore, in codon 1274.

Continue Reading.

Normal prion protein regulates iron metabolism

An iron imbalance caused by prion proteins collecting in the brain is a likely cause of cell death in Creutzfeldt-Jakob disease (CJD), researchers at Case Western Reserve University School of Medicine have found.

The breakthrough follows discoveries that certain proteins found in the brains of Alzheimer’s and Parkinson’s patients also regulate iron. The results suggest that neurotoxicity by the form of iron, called redox-active iron, may be a trait of neurodegenerative conditions in all three diseases, the researchers say.

Further, the role of the normal prion protein known as PrPc in iron metabolism may provide a target for strategies to maintain iron balance and reduce iron-induced neurotoxicity in patients suffering from CJD, a rare degenerative disease for which no cure yet exists.

The researchers report that lack of PrPC hampers iron uptake and storage and more findings are now in the online edition of the Journal of Alzheimer’s Disease.

“There are many skeptics who think iron is a bystander or end-product of neuronal death and has no role to play in neurodegenerative conditions,” said Neena Singh, a professor of pathology and neurology at Case Western Reserve and the paper’s senior author. “We’re not saying that iron imbalance is the only cause, but failure to maintain stable levels of iron in the brain appears to contribute significantly to neuronal death.”

Prions are misfolded forms of PrPC that are infectious and disease-causing agents of CJD. PrPc is the normal form present in all tissues including the brain. PrPc acts as a ferrireductase, that is, it helps to convert oxidized iron to a form that can be taken up and utilized by the cells, the scientists show.

In their investigation, mouse models that lacked PrPC were iron-deficient. By supplementing their diets with excess inorganic iron, normal levels of iron in the body were restored. When the supplements stopped, the mice returned to being iron-deficient.

Examination of iron metabolism pathways showed that the lack of PrPC impaired iron uptake and storage, and alternate mechanisms of iron uptake failed to compensate for the deficiency.

Cells have a tight regulatory system for iron uptake, storage and release. PrPC is an essential element in this process, and its aggregation in CJD possibly results in an environment of iron imbalance that is damaging to neuronal cells, Singh explained

It is likely that as CJD progresses and PrPC forms insoluble aggregates, loss of ferrireductase function combined with sequestration of iron in prion aggregates leads to insufficiency of iron in diseased brains, creating a potentially toxic environment, as reported earlier by this group and featured in Nature Journal club.

Recently, members of the Singh research team also helped to identify a highly accurate test to confirm the presence of CJD in living sufferers. They found that iron imbalance in the brain is reflected as a specific change in the levels of iron-management proteins other than PrPc in the cerebrospinal fluid. The fluid can be tapped to diagnose the disease with 88.9 percent accuracy, the researchers reported in the journal Antioxidants & Redox Signaling online last month.

Singh’ s team is now investigating how prion protein functions to convert oxidized iron to a usable form. They are also evaluating the role of prion protein in brain iron metabolism, and whether the iron imbalance observed in cases of CJD, Alzheimer’s disease and Parkinson’s disease is reflected in the cerebrospinal fluid. A specific change in the fluid could provide a disease-specific diagnostic test for these disorders.