Prions: What We Know About Proteins That Kill 

Posted onJuly 20, 2021 in Medical news

PROTEIN IS THE MAIN BUILDING MATERIAL OF THE BODY and an invariable component of a healthy diet. Although proteins have always worried researchers, today the attention of the latter has switched to a special kind – prions. On the Internet, whatever they call them: “ideal killers”, “the key to immortality” and even “zombie molecules”. The scientific community is racking its brains over how to use proteins that can rapidly and inevitably destroy the brain, for the benefit of humanity. We decided to figure out what prions are and asked experts how killer proteins could potentially be useful for humans.

Why people started talking about them

They began to study prions, because they are the cause of rare, but very dangerous diseases of humans and animals. These include the so-called mad cow disease, pruritus of sheep and, for example, lethal familial insomnia , in which a person practically stops sleeping and dies within 12-18 months against the background of progressive dementia. Another example of prion disease – disease of Creutzfeldt – Jakob disease , leading to death within six months or a year after the onset of symptoms; the disease affects the brain, therefore, memory and attention disorders develop, and then coordination disorders and seizures. The latter is included in the list of the most dangerous        diseases in the world, because doctors simply do not know what to do with it. It all started with the mysterious kuru disease in Papua New Guinea, for which there seemed to be no rational explanation.

How they were discovered

The story of the discovery of prions draws on an adventure film with elements of fantasy: it would seem, what could be healthier than life on a beautiful island in the middle of the ocean, for example, in New Guinea? But once upon a time a disease of an unknown nature fell upon the Fore people who lived there, which manifested itself as a very strong shaking that prevented a person from first walking, then standing and sitting. In the end, all the patient was capable of was to lie down and tremble. Paralysis followed, followed by death. For its unusual clinical manifestations, the locals called the disease kuru (translated as “shivering”). Pediatrician and virologist Carlton Gaidushek went to New Guinea to study infectious diseases, including the mysterious kuru. Everything worked out for him: in 1976, Gaidushek received the Nobel Prize “for discoveries concerning new mechanisms of the origin and spread of infectious diseases,” sharing it with Baruch Blamberg, who discovered the hepatitis B virus.

However, Gaidushek did not discover the prions themselves – he only suggested that the virus causes a “pathogenic particle” that is not visible under a microscope. To do this, the scientist had to spend a long time on the island, dissect a couple of hundred deceased representatives of the handicap and even send their organs (especially Gaidushek was interested in the brain, which acquired a spongy structure in patients) to his colleagues from different countries. The cause of the epidemic among the Fore people was ritual cannibalism: it was practiced even after the official ban of the authorities. The motives are prosaic: Foret believed that along with eating the flesh of a deceased person, his mind, abilities or talents would pass to them.

What is it all about

At first, scientists thought they had found a new virus or viral particle. Prions are really similar to viruses in that they do not have a cellular structure – that is, they do not consist of cells, unlike bacteria. In this case, the virus is a nucleic acid, that is, DNA or RNA, in a protein envelope. But when prions were exposed to agents that destroy these acids, dangerous infectious qualities persisted. Gradually, it was concluded that a prion is just a protein, only with an unusual structure. All protein molecules have a certain three-dimensional configuration – to simplify greatly, this is how a chain of amino acids is stacked in space. Well, in prions this structure is abnormal; surprisingly, given the “usual” chemical composition, it is this anomaly of configuration that makes the prion deadly.

How Normal Protein Is Made Abnormal

The name of the anti-human proteins was given by the American physician Stanley Pruziner. By combining the words protein and infection, he obtained “prions”, designated them as the newest type of biological infectious agents, and for the first time described their principle of action. In 1997 he received the Nobel Prize for his work. Prusiner also discovered a protein that generates prions – it was called a prion protein, PrP. The most interesting thing is that the gene encoding PrP is contained in the twentieth chromosome of a person – that is, it is present in the DNA of any of us. But the chance of its transformation into a prion is minimal, and most people live peacefully without the risk of prion diseases. However, just one mistake in protein synthesis can lead to the conversion of normal PrPC to abnormal PrPSc.

As Valery Ilyinsky, geneticist and CEO of Genotek, explains, prions are ordinary proteins that have acquired an unusual structure. This allows them to change the structure of similar proteins, also turning them into prions, a process similar to infection. For the onset of the disease, the manifestation of the first damaged protein is necessary – this can occur either as a result of a spontaneous error in its synthesis, or after the ingress of a prion from the outside, from another person or animal. And then a chain reaction starts.

Rustam Ziganshin, Ph.D. in Chemistry, notes that the reason and mechanism of transformation of the “normal” form of prion protein into a dangerous one is very poorly understood today. In in vitro (in vitro) experiments, this transformation requires various additional factors. At the same time, in experiments on animals, prion diseases developed when a “normal” prion protein was injected into mice that were completely devoid of its programming gene. It is not clear what caused him to become “aggressive” in this case

Eternal youth or inevitable death

Now they started talking about the fact that, for example, Alzheimer’s disease or Parkinson’s disease may be associated with the prion mechanism. If so, then we can expect the emergence of new methods of treatment or prevention of these serious diseases. Interestingly, yeast proteins are similar in their mechanism of action to prions – it is quite possible that yeast will help in the study of these strange molecules. There is also talk that it is prions that will help find a cure for various malignant tumors or HIV infection, and indeed will become a “philosopher’s stone” that will lead humanity to eternal life or eternal youth. However, while these statements are unfounded.

Rustam Ziganshin explains that, like any research in the field of biology, the study of prion proteins expands the boundaries of our knowledge of living things. From a practical point of view, the results can help to understand how a number of dangerous, as yet incurable, diseases develop. Perhaps we will get a tool to deal with them. If we understand how an abnormal protein is obtained from a normal protein, and learn to control this process, then maybe we will be able to start it in the opposite direction – that is, turn pathological proteins into healthy ones, and with them restore health to tissues and organs.

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