Prion diseases of the nervous system: basic information

Prion diseases are a special kind of severe neurodegenerative diseases of man and animals that are caused by special pathogens: prions. Basic information about prion diseases of the nervous system, that is: what do prions represent themselves, how they cause defeat of the nervous system, what diseases cause and how to deal with them, you can learn from this article.

What are prions?

Prions are protein structures. These protein molecules can be normal, forming part of human and animal tissues, that is, contained in the body of healthy people and other mammals, and may be pathological, causing disease.

It was previously assumed that any "living" structure necessarily contains nucleic acids (DNA, RNA) that allow it to multiply. All viruses, bacteria, fungi, birds, animals, humans contain nucleic acids. And it was assumed that the absence of these acids means the impossibility of reproduction, but the discovery of prions turned these ideas.

Prions consist only of protein, but they can reproduce. Getting into the body, they cause the transformation of the normal prion contained in it into a pathological one, thus increasing its quantity in this way. That is, all cases of collision with normal prions of the organism result in the formation of pathological prions. This takes a much longer time than with the multiplication of viruses or bacteria, so from the moment prion gets into the body before the development of the disease, it takes years.

Prions were discovered in 1982 by Stanley Prusiner, for which in 1997 he was awarded the Nobel Prize.

Prior to the discovery of prions, a number of human and animal diseases were described, the cause of which could not be established. As early as the 18th century, the so-called "scrapes" of sheep with symptoms in the form severe itching, movement disorders in the limbs and seizures, which indicated the defeat of the nervous system. So, in 1957, American Carlton Gaydushek described the disease in the tribe of the Fore, who lives in the high mountains of Papua New Guinea. The disease was associated with cannibalism and was thus transmitted from one person to another. Since 1986, in England, and then in other countries, the disease of a large horn cattle, called "cow rabies" (although to the causative agent of rabies it had no relations). "Mad cow disease" took on the dimensions of the epidemic and was caused by prions. In the 1990s, the transfer of "mad cow disease" to a person along with the meat of a sick animal was proved. To date, the study of a number of diseases with unidentified causes has led to the fact that hypothesis about prion nature of these diseases (for example, Alzheimer's disease, Parkinson's disease and others). Despite the progress in this direction, a lot still remains beyond the bounds of the one comprehended.

Properties of prions

Prions are very stable connections. Most methods of decontamination and disinfection are ineffective in controlling them. They do not die during boiling for 2-3 hours, withstand the cold to -40 ° C for several years, are not sensitive to ultraviolet radiation and radiation, are not inactivated by formalin treatment.

The special structure of prions leads to the fact that the body does not know how to deal with them. The human body does not produce antibodies (humoral immunity) against them, does not attack prion lymphocytes (cellular immunity), as if it does not notice them. That is, the entry of prions into the body inevitably leads to the development of the disease. Even with a 10-millionth dilution, prion is contagious to humans.

How can I get prions?

To date, there are three methods of infection:

• transmissible: when transferring a prion from one species of mammal to another. And if earlier it was said about the existence of interspecific barriers, that is, the transfer from a cow or a sheep to a man was denied, that prions can be transmitted from any infected animal or person (theoretically), and the possibility of infecting humans from cows and other rights. The cause of the pathological prion can be eating meat of a sick animal, using biological tissues of animals and humans (blood preparations, transplantation of the cornea or dura mater and that similar). It is believed that different biomaterials have a different degree of pathogenicity. Thus, the most contagious are the tissues of the brain and meninges, in view of the highest content of prions in them, then - blood and its preparations. The ingestion of the pathogen under the skin and through the mouth (with food) is attributed to the least contagious ways. This means a certain dose-dependence of prion diseases;
• hereditary: when the disease develops as a result of a gene mutation that occurs in a specific area of ​​the 20th chromosome. A special section of the 20th human chromosome is responsible for the presence of a normal prion protein in the body. Its functions are not fully understood. In the event of gene disorders, instead of normal prion, a pathological, causing disease is synthesized;
• sporadic: spontaneous occurrence of abnormal protein in the human body.

Thus, it becomes clear that prion diseases can be both infectious and hereditary. Whichever way a prion emerges in the human body, it can cause another person's infection. This means that even a randomly generated prion disease can be transmitted to another person transmissively. A different degree of infectivity of prions is suggested, which arose as a result of mutation or spontaneously, and also received from another species of mammals.

What causes prions in the body?

Prions can cause so-called spongy (spongy) encephalopathies, that is, damage to the central nervous system. Morphologically it means:

• the formation of cavities in the brain cells ("holes which is why the notion of "sponginess" was formed);
• death (degeneration) of neurons;
• proliferation of connective tissue in place of dead nerve cells;
• atrophy of the brain;
• the formation of amyloid plaques (the latter are formed from clusters of pathological prions).

And all this arises against the background of a complete absence of any inflammatory reactions.

What diseases are prion in humans?

To date, it is known for certain diseases of man, whose wine is the prions:

• Creutzfeldt-Jakob disease;
• the Gerstmann-Streussler-Sheinker disease;
• Kuru disease;
• family fatal insomnia (insomnia);
• chronic progressive spongiform encephalopathy of childhood (Alper's disease).

Creutzfeldt-Jakob disease

This disease affects the human nervous system, makes it disabled and leads to the development of dementia.

This type of prion infection is quite diverse, because at present it is customary to single out several of its forms:

• sporadic (classical);
• family (hereditary);
• iatrogenic;
• a new atypical form, resulting from infection with meat of cattle, stricken "rabies cow that is, this form is an analogue of "cow rabies" in humans.

Sporadic formsince the description of this disease in the 20s of last century was the most common (about 85-90% of all cases of Creutzfeldt-Jakob disease). It occurs mainly in old age, the first signs appear after 55 - 60 years. However, in recent years, statistics have changed since the epidemic of "cow rabies". More and more cases of a new atypical form started as a result of infection from cows. This form is characterized by an earlier appearance: young people become ill. Incidence of sporadic form is 1 case per 1 million population per year. Characteristic is the gradual appearance of various symptoms, which are divided into two groups: neurological and mental. The appearance of these or other changes is determined by the area of ​​damage in the brain. Initial symptoms can be: headache, dizziness, sleep disturbance, decreased sexual desire, anorexia, general weakness and fatigue. Gradually deterioration of memory and attention develops, disturbance of thinking, loss of sight, depression, emotional lability. Mental disorders can also occur quite acutely in the form of episodes of disorientation, hallucinations and delusions. From the neurological symptoms, muscle weakness in all the limbs (pareses) is formed, muscle tone builds up, speech is broken up to the total loss, there is a pronounced coordinating instability (ataxia), involuntary movements in the extremities may occur (especially myoclonus: fast, non-rhythmical small-amplitude contractions of small muscles), as well as convulsive syndrome. The disease progresses steadily and in the final stage leads to immobility, loss of control over the function of pelvic organs, dementia and cachexia. Life expectancy from the moment of appearance of the first symptoms is no more than 2 years. The outcome of the disease is death in 100% of cases.

Family formis associated with gene mutations in the region of the 20th chromosome. It accounts for about 5-6% of all cases of Creutzfeldt-Jakob disease. The disease is autosomal dominant, which means that it is not related to sex, and that the pathological gene manifests itself always, regardless of whether the second analogous gene is normal (all human genes - paired). The first signs of the disease occur about 5-10 years earlier than in the sporadic form. In the rest the course of the disease is similar to the previous form.

Iatrogenic formoccurs as a result of infection of a person during medical interventions. Statistics of this form of the disease is absent, since it is quite difficult to trace and prove just such a path of infection. There are documented cases of infection when using a dura mater, cornea, stereotaxic operations on the brain (mainly these cases refer to France and Australia). The incubation period (the time from prion infection to the appearance of the first signs of the disease) ranges from 7 months to 12 years. The duration of the incubation period depends on several factors: the location and mode of penetration of prions into the body, the dose of the causative agent, the initial genotype of the human body. The fastest disease develops when prions directly enter the brain tissue during operative interventions, a slightly longer incubation period for infection as a result of a dural transplant and cornea. The ingress of prions into the body with the introduction of infected drugs (eg, human gonadotropin) is accompanied by the development of the disease in 5-10 years. For this form of the disease is characterized by the prevalence of neurological symptoms over the mental. Also, expressed cerebellar ataxia, speech disorders, changes in muscle tone, myoclonus develop. Invariably developing dementia. Patients die within one - maximum 2 years.

"Mad cow disease" in people,or a new atypical form of Creutzfeldt-Jakob disease began to acquire relevance after the epidemic of prion infection in cattle in England in the 90's. The consumption of meat of affected animals caused the infection with prions. This form of the disease is characterized by a much earlier start: cases are recorded at 30 and 40 years. As with iatrogenic form, neurologic manifestations predominate over psychic manifestations. However, this does not affect the forecast. This form of the disease is also fatal to humans.

The disease of Gerstmann-Streussler-Scheinker

This variant of prion disease belongs to the hereditary. It occurs quite rarely: 1 case per 10 000 000 population. Transmitted by autosomal dominant type. Usually the disease manifests itself in the patient's age about 40 years. The first and dominant in the clinical picture are cerebellar disorders. At first, there is dizziness and unsteadiness in walking. Coordinating violations progress, arbitrary movements become redundant and "missed gradually independent walking becomes impossible. Along with these symptoms, there are violations of muscle tone, hearing loss down to deafness, decreased vision to blindness, look up (when a person can not look up simultaneously with two eyes), problems with swallowing and sound reproduction. Dementia appears in the terminal stage of the disease. The average life expectancy is from 2 to 10 years. The outcome of the disease is death.

Illness of the kuru

This species of prion infection has been studied through a tribe of cannibals living in the high mountains of Papua New Guinea. Until 1956, the traditions of ritual cannibalism were widespread among the population of this geographical zone: the eating of the brain of deceased relatives. It is assumed that one of the members of the tribe sporadically a prion infection, which then spread due to the devouring of his brain by his fellow tribesmen. After the cannibalistic cancellation of the tradition, the disease began to be registered much less frequently, to date, almost never occurs. The infectious onset of the disease and infectiousness were proved by Gaydushek by infecting chimpanzees with an extract from the brain of sick people.

"Kuru" in the language of this tribe means "laughing" or "trembling with fear." This name is not accidental. After an incubation period of 5 to 30 years, cerebellar disorders develop with the trembling of individual body parts and uncontrolled laughter, greased speech, impaired eye movements, dysfunction swallowing, muscle weakness. Thinking in the beginning is not violated, dementia develops already in the terminal stage. Patients live 4 to 36 months after the onset of the first symptoms.

Family fatal insomnia

This prion disease is known to science since 1986. It is very rare. Refers to hereditary diseases with autosomal dominant type of transmission. By 2003, 26 families with familial fatal insomnia had been described. Has a fairly variable age of onset of the disease: from 25 years to 71 years. Life expectancy from the moment of appearance of the first signs is from 6 to 48 months.

Insomnia becomes the main symptom of the disease. The human body loses its ability to regulate the cycles of wakefulness and rest, can not sleep at all. In addition to insomnia, there are motor disorders in the form of myoclonias, tremor, and muscle weakness. Typical are vegetative disorders, manifested by increased blood pressure, fever, sweating, palpitations. From mental disorders, visual hallucinations, panic fears, episodes of confusion are possible. On the background of a complete lack of sleep, exhaustion begins and the patient dies.

Chronic progressive spongiform encephalopathy of childhood (Alper's disease)

This type of prion diseases develops in children (up to 18 years). Characterized by inheritance transfer by autosomal recessive type (not related to sex and manifested only if two pathological genes coincide from father and mother). The defeat of the nervous system is a violation of vision, the development of epileptic seizures. Possible periodic acute conditions, proceeding according to the type of strokes. In addition to the defeat of the nervous system, this disease is accompanied by liver damage. Quite quickly develops chronic hepatitis, which passes into cirrhosis. Patients die from intoxication due to severe hepatic insufficiency within 12 months from the onset of the disease.

Treatment of prion diseases

Unfortunately, at present, all prion diseases are not curable. Patients receive symptomatic therapy (for example, anticonvulsants in epileptic seizures), which can only alleviate suffering, but does not affect the prognosis in any way. And he is very disappointing: all known prion infections are deadly to humans.

How to protect yourself from prion infections?

From the development of spontaneous and hereditary forms of prion infections, one can not protect oneself. Theoretically, some hereditary forms can be excluded (it is meant to determine whether there is a similar genetic disorder in a particular person) after having undergone genetic diagnosis. However, it is very difficult to carry out this, because the laboratories carrying out such analyzes can be found mainly abroad.

In order to somehow protect yourself from Creutzfeldt-Jakob disease, in the first place, it is necessary not to eat Meat and meat products from regions where cases of bovine disease have been reported (mainly, countries Europe. In Russia, there is a ban on the import of such products from "dangerous" regions). Also, do not take medicines made from human and animal blood (replacement is necessary for synthetic analogs), avoid blood transfusion whenever possible.

Thus, prion diseases are insufficiently studied forms of infectious and hereditary disorders that arise in the human body as a result of the appearance of pathological prions. In most cases, prion diseases affect the nervous system. The result of the disease is always the same: death. While modern medicine does not have effective means of combating these diseases.

TV channel "Russia-24 scientific and educational program "Prions - little killers". Adriano Aguzzi is the director of the Swiss Institute of Neuropathology, which studies prions.