What Is Jacobs Syndrome?

Prions, also known as prions, protein infectious factors, poisonous tadpoles or infectious proteins, are a class of small molecule non-immune hydrophobic proteins that can infect animals and replicate in host cells.

It is not appropriate to use prions to name prions. The biological characteristics of prions are very different from viruses. The discovery of prions suggests that

Prions, like conventional viruses, are filterable, infectious,

As early as three hundred years ago, humans first discovered diseased animals infected with prion disease in sheep and young goats. Due to the strange itchiness of the sick animals, they often rub on the rough trunk and the stone surface, so that the hair on the body is abraded, and it is called "sheep pruritus". The disease is widely spread in Europe and Australia, with an incubation period of 18 to 26 months. The affected animals are excited, lose coordination, stand unstable, itch, paralyze until death. Later found infectious

Since there is no effective treatment for prion disease, it can only be actively prevented. The main methods are:

Eliminate known infected animals and properly isolate patients

It is forbidden to eat contaminated food.

There is no clear answer yet. Because it has been shown that prion disease infection between different animals is related to the degree of prion protein amino acid differences. The high incidence of mad cow disease is closely related to the presence of prion-bearing sheep tissues in cattle feed additives. There are 7 amino acid differences between prion proteins of cattle and sheep, and 16 amino acids difference between hamsters and mice, which makes it difficult for mice to be infected with hamster prions. There are more than 30 amino acid differences between cattle and humans, which are far greater than the differences between hamsters and mice. It seems that Mad Cow Disease cannot be transmitted to humans. But it has been confirmed that human prion can infect mice. The human and mouse PrP genes are 28 codons different; two farmers in the UK who have "mad cow disease" cattle have died of Creutzfeldt-Jakob disease. Of the four newly discovered patients in the UK, three of them live in areas with frequent BSE. Therefore, the possibility of spreading mad cow disease to humans cannot be ruled out. ^[1]

Since prion protein (PrPc) cannot cause disease by itself, it must be transformed into prion (PrPsc) in order to damage neurons. This change is precisely caused by prion stress. That is, a pathogenic molecule first binds to a normal molecule. Under the action of the pathogenic molecule, the normal molecule turns into a pathogenic molecule, and then the two pathogenic molecules bind to two normal molecules respectively, and then the latter turns into a pathogenic molecule. Disease molecules. Repeatedly, the disease is multiplied by the domino effect. It can be seen that there are two basic conditions for disease, one is prion, and the other is prion protein.

Are the above assumptions valid? The answer is yes. Animal experiments have shown that prion vaccination can make animals sick. Mice that have been genetically engineered to remove prion genes will not be infected even if prions are introduced.

Human Gestmann Syndrome and fatal familial insomnia have been determined to be genetic due to mutations in the gene encoding the protein. These mutations render the encoded protein structurally unstable and easily convert to prions . Dozens of transmitted families have been identified. 10-15% of Creutzfeldt-Jakob disease syndromes are caused by genetic mutations, and more than a hundred transmitted families have been identified. Kuru disease is identified as an infectious disease. ^[1]

The prion disease-causing "protein-conformational pathogenic hypothesis" proposed by Pruena in 1982 was gradually improved by Weissmann and others. The main points are as follows: Prion proteins have two conformations: cellular (normal PrPc) and pruritic (pathogenic PrPsc). The main difference between the two is their spatial conformation. PrPc only has -helix, and PrPsc has multiple -sheets. The latter has low solubility and is resistant to proteolysis. Prpsc can force PrPc to transform into Prpsc, achieve self-replication, and produce pathological effects; Gene mutations can cause cellular PrPc The -helix structure is unstable, and spontaneous transformation occurs to a certain amount. The -sheet layer increases, eventually becoming Prpsc type, and the disease is multiplied by the domino effect.

From this hypothesis, we can know that: 1. Prions are proteins without DNA, RNA and other components that we usually think of as genetic material; 2. Corresponding to prions are proteins with normal functions, which means prions are normal The formation of protein spatial structure variation.

Since prion does not have its own genetic information, its genetic information must be derived from the nucleus of its "host". Therefore, prions are actually formed by encoding the genetic information of the "host" itself. The genetic information encoding prions is at least the same in the chromosomal genes of the nucleus, but after the formation of the polypeptide chain, it has to undergo a series of modification processes. One may be that some of these modification processes have errors and cause normality. The spatial structure of the protein mutates into an abnormal structure. The second possibility is that there was no error in this modification process, but after the normal protein was formed, the normal protein mutated due to external factors, making it a so-called "prion".

Therefore, we can define "prion" as the formation of a protein's spatial structure during normal protein production, or after normal protein production, due to a certain abnormal factor!

With the above definition, we continue to discuss the infectivity of prions. According to the conclusion of the American scientists published in the "Cell" magazine in 2005, the use of a small number of "prion" molecules can turn a large number of normal proteins into "prion", that is, a small number of mutated protein molecules can change the normal configuration Proteins become mutated molecules. This explains why the small amount of prions can cause the body to lose its function.

From the essence of prion, it is a normal protein whose spatial configuration is changed, which is caused by denaturation of normal protein.

There are many types of proteins in animals and their functions are very different. Denaturation of each protein will lead to the loss or weakening of its original function. Due to the fragility of the nervous system, the degeneration of a certain protein tissue can cause great damage to the entire system, leading to disease.

It has been discovered so far that not all prions are dangerous. In fact, they exist in many plants and animals. Because of this, scientists believe that these deformed proteins may have some benefits for their hosts. This hypothesis was confirmed during research on a particular moss. Normally, when the moss in one place and the moss in another place are long enough for their outer cells to contact each other, the virus will spread from one part of the infected moss to another part without the infected moss. However, prion protein seems to go around the edge of the infected moss-this can cause cells in the edge of the moss to die, creating a barrier that prevents the virus from passing through and protecting the moss from contamination.

In 1965, Dr. Brian Cox discovered a strange inheritance in yeast that involves only proteins, and they called it the [PSI +] element ([PSI +] element). year 1994,

The research on prions focuses on two aspects.

First, the molecular structure, genetic mechanism, proliferation mode, interspecific barriers of transmission,

Research on prions has won the Nobel Prize in Physiology or Medicine twice in the past 20th century Nobel Prize in 1976 and 1997.

In the early 1950s, a Fore tribe living in the Papua New Guinea Plateau of Oceania is still in the primitive society. They have been following a religious carnivorous habit. A few years later (usually 5-30 years), carnivores Quite a few people will develop tremor that eventually develops into aphasia until they can't move at all, and all infected people die within a year. The tremor of modern medicine is called "Kuru" in the local dialect. Fore tribe had 160 villages and 35,000 people. 80% of the people suffered from the disease during the epidemic, and the entire nation was in danger. In the late 1950s, the bad habits of people eating were banned under the intervention of the World Health Organization and the Australian Government, and the incidence gradually declined. Gajdusek and Gibbs of the National Institutes of Health and Zigas of Australia have collaborated to study this tremor disease, and a series of experiments have confirmed that tremor, pruritus, and Alzheimer's disease belong to the same pathogen. Gajdusek obtained from this 1976 Nobel Prize in Physiology and Medicine. Since then, scientists from various countries have done a lot of research on tremor, and found that tremor is a chronic degenerative disease of the nervous system. Its pathological changes are similar to those of spongiform encephalopathy in animals, and animal models have been successfully constructed.

Stanley BPrusiner, a neurology expert at the University of California, USA, proposed that prion is an infectious protein particle that does not contain nucleic acids and can replicate itself. Prusiner won the 1997 Nobel Prize in Physiology and Medicine for his research on prions. ^[1]