Prions ( from the English. Proteinaceous Infectious particle and the analogy to virion ) are proteins that may be present in both normal ( physiological ), but also abnormal and disease-causing ( pathogenic ) structures ( conformation) in the animal organism. So this is not about being but to organic poisons (toxins ) with virus-like properties.

The pathogenic prions are likely to Creutzfeldt -Jakob disease in humans, BSE ( " mad cow disease " ) in cattle and scrapie ( scrapie ) in ovine responsible. However, this could not yet be proven safe. 2007 resulted in new doubts about whether the content of a tissue of pathogenic prions in each case correlates with its infectivity.

Pathogenic prions enter either through contaminated food ( this is the most likely route of infection, but other routes of infection such as the smear infection could not be excluded ) in the body (eg BSE, Chronic Wasting Disease or Kuru ) or they are created by the spontaneous refolding of endogenous prions ( eg familial variant Creutzfeldt -Jakob disease, familial insomnia).

Generally pathogenic prion by other pathogens such as viruses, bacteria or fungi, can be distinguished, since they do not contain DNA or RNA. They are not only of great scientific interest, but had by the ' BSE crisis ' and the new variant of Creutzfeldt -Jakob disease also have strong effects on areas such as agriculture, consumer protection, medicine and politics.

Have physiological (ie, normal or non-pathogenic ) prions to 43% of the structure of alpha- helices. The pathogenic forms but there are only about 30 % of alpha -helices, 43% of them are made of beta-sheet structures. The risk of pathogenic prion consists in the fact that they are able to convert the physiological, non-pathogenic prions in pathogenic.

The normal prions are increasingly present in the brain tissue, causing the operations just described can have a profound and serious consequences for the of the pathological prion affected ( to ) training organism (see pathology and symptoms). New research by the U.S. researcher Susan Lindquist that prions play an important role in neurogenesis ( development of new nerve cells in the brain).

The simplified prion hypothesis and characteristics of prion diseases

One of the many occurring in animal and human body protein called PrPC ( cellular prion protein = cellular prion protein). It is found mainly in the nervous system, especially in the brain. The prion would more or less differ slightly between the different animal species and possibly also within one species. PrPC is mainly found on the cell surface and protects cells from divalent copper ions, H2O2 and free radicals. Furthermore, it is assumed that it is one of the first sensors in the cellular defense against reactive oxygen species and free radicals, and has effects on the enzymatic degradation of free radicals. Device of this normal protein PrPC into contact with a named protein PrPSc ( prion protein scrapie pathogenic form of the prion protein, which was found in the form first in diseased animals scrapie ), PrPc takes the form of PrPSc, " it works to "it changes its conformation. It develops a chain reaction in which more and more PrPC is converted to PrPSc. Large amounts of PrPSc but destructive act on the brain, because they are insoluble and are deposited in the cells. As a result, these cells die off; holes may be formed in the brain, a sponge-like structure. Hence the name of this disease: spongiform encephalopathy, spongy brain disease. Prion diseases always end fatally.

The initiation of the disease can occur in three ways, which is unique among all diseases:

The familial forms of prion diseases can be transmitted in the experiment, for example, can the resulting in a person due to the genetic disposition PrPSc trigger the disease in mice when it was previously injected into the brain.

Prions are highly resistant to conventional disinfection or sterilization process, which was also a reason for the iCJD cases and the BSE crisis. Today there are the more difficult inactivation of prions tuned strict rules for the sterilization of material that has come into contact with potentially prionhaltigem tissue.

The prion hypothesis is now regarded as relatively secure. That in addition to the PrPSc yet another factor plays a role, but can not be definitively excluded. After the intense search for viruses, viroids or nucleic acid remained ever unsuccessful, there are hardly any scientists who pursue this path. In public, occasionally circulate outsider opinions such as the Organophosphattheorie, is after the BSE related to insect venoms, but for which there is no scientific evidence.

History of prion research

Individual prion diseases have been described long ago ( scrapie, the prion disease of sheep in 1759 by Leopoldt; CJD 1920 by Creutzfeld ), could without one knew anything about the cause of these diseases or classify them into a group. After 1932, the transferability of scrapie detected and 1957 Kuru was described for the first time, the similarity of these diseases was found and Kuru also transmitted experimentally to monkeys in the 60s. Although there were first indications of a nucleic acid- free agent, it was generally most of lentiviruses as causative factors.

Published 1982 by Stanley Prusiner " prion hypothesis " was first recorded in the critical science, as a nucleic acid- free infectious agent by then was unimaginable. In retrospect, however, this hypothesis proved to be groundbreaking and 1997 Prusiner was honored for his work in the field of prion research with the Nobel Prize. In the years after the establishment of this hypothesis, evidence for the correctness of this hypothesis could be obtained in numerous experiments, but no definitive proof. In 1986 the BSE epidemic in Great Britain, 1996, the first cases of vCJD have been reported. Politicians tried to make up for their failures in prevention and consumer protection, among others, by generous expenditure in the field of prion research. Several working groups have been newly furnished, built centers and established partnerships; the number of people who dealt with prions, rose sharply. This reinforces provided in the wake of the BSE crisis of the policy money led to advances in prion research, otherwise not at this rate could be achieved.

Structure of the prion protein

It is a human of 253 amino acids (aa ) composed glycoprotein which is encoded in the prion protein gene ( PRNP ). The AS- homology to other mammals is 85% or more, between cattle and humans, there are for example 13 AS- differences. In each case, one or more mutations known to cause fCJD, GSS, or FFI. At codon 129 is a methionine / valine polymorphism, a crucial factor in disease onset and course. PrPC contains the large proportion alpha helices PrPSc more beta -sheet structures, but both contain the same primary amino acid sequence. The exact procedure of the " refolding " of PrPC into PrPSc is still unknown. This changes the properties of the prion protein that is PrPSc poor water soluble ( as the hydrophobic chains are not, as is customary in the α -helix, showing the inside of the protein tertiary structure ), as far as possible resistant to many disinfectants, ionizing and ultraviolet radiation, stable to heat ( moist heat ( 131 ° C)) in used for sterilization in medicine autoclave destroyed the PrPSc after two hours, so that medical instruments in succession must be autoclaved four times, using dry heat, the prion is at 200 ° C for 60 minutes after inactivated) and by proteases stodgy ( a protein proteases are best in the unfolded state " cut ", but the denaturation in the body is worse possible) by the change in secondary structure. PrPC is mainly localized at synapses. The PrPC play a role in the formation of blood - forming stem cells (see below), according to the latest findings. Prion protein knockout mice show a slower recovery after a stroke, in addition, the mice are prone to obesity. However, there is evidence of a role as a copper- binding protein at the synapse. According to a publication by U.S. researchers in the journal PNAS maintain normal prion proteins, the regenerative capacity of hematopoietic stem cells. In these cells occur prions in the cell membrane and apparently not fulfill important tasks - at least as long as the body is healthy.

Pathology and symptoms of prion diseases

Prion diseases are characterized primarily by motor symptoms such as ataxia and ( most notably in humans) cognitive problems to dementia. After an incubation period of years to decades, the disease always end fatally. In the brain are found in the neuropathological assessment under the light microscope cancellous ( spongy ) changes and, depending on the disease, various distinct deposits such as amyloid, kuru plaques and florid plaques.

Selection of current research areas

Function of PrPC; exact structure of PrPC and PrPSc; Transmission paths; Blood (rapid ) test; Treatment options; Opportunities for prevention, risk assessment and monitoring, and the prion -associated proteins by 2D gel electrophoresis to clarify the pathogenesis of PrPc to PrPSc. It is believed that the infection with the prion disease is carried out by a prion -associated proteins, and not by the actual prion protein.