Prions Essay, Research Paper

PRIONS

Prions have been a mistery for scientists from the day they where discovered. Prions act like viruses but they are not. Their structure and chemistry are unknown. They are believed to be proteins but that is yet to be completely proved.

Prion stands for proteinaceous infectious particles . Prions are known to cause many diseases involved with nervous systems like the brain. They are the ones that cause the well known mad cow disesase in Britain and scrapie for animals. For humans they are known to cause a rare disease in Papua New Guinea called Kuru ( or laughing death ) which striked only the cannibals in the Highlander tribes. Investigation led to the discovery of prions inside the of the victims brains that were eaten by the tribesmen that when they died, as a sign of respect their brains where eaten and the chain went on and on.

The thing that makes prions so special is the fact that they lack the basic elements for reproduction, deoxyribonucleic acid and ribonucleic acid DNA and RNA respectively. This is what has given science a great deal of doubt as this would give the dogma of the beginning of live a radical turn.

Prions have been in research for many years with experiments like the one done by Stanley B. Pruiser and his team of scientists at the School of Medicine of the University of California at San Francisco in which a study was carried out on mice to see if he was able to purify the scrapie agent ,another prion disease, in mice. But mice as humans took very long to develope the disease, for example Gerstmann-Straussler-Scheinker disease or fatal familial insomnia, which appear mostly on humans which have passed the age of forty and only in very rare cases before, so the experiment was changed to hamsters as these die faster because developed the disease earlier. One of the methods used for this purification process was using a centrifuge, that separates the component of a mixture according to their size and density. After a decade of experiments using the centrifuge method and other chemical methods, several discoveries were made : It was found out that the infectious particles were extremely heterogencous in s

ize and density, the scrapie agent can be found in many molecular forms and the biological activity of the scrapie agent depends on a protein (PrP, called later when discovered it was a single molecular specie protein). This protein was found to be a glycoprotein (PrP): sugars are bounded to the amino acid, and it is half the size of hemoglobin. PrP is the protein, but we can also find today PrPc (for cellular) and PrPsc (for scrapie). Prp can be found in steak ( skeletal muscle) and also on the surface of lymphocytes present in milk, but there is no evidence that the ingestion of this things can cause disease in humans , but there is the still a risk.

Amyloid hypothesis.

Prions were found to form rods: long fibrils in brain tissues infected with scrapie and Creutzfeldt-Jacob disease. They believed that the fibrils can be distiguished from amyloid; that they represent a filamentous animal virus causing scrapie and that they are elongated form of prion rods.The most impotant aspect of these rods is the resemblance to amyloid. Amyloid plaques in the central nervous system form considered accumulations of waste formed as some sort of a disease process. This plaques are believed to be aggregations of prions in an almost crystalline state. The production of antibodies to PrP allowed to demonstrate that amyloid plaques in the brain of scrapie-infected hamsters contain prion proteins. This amyloid plaques have been found on Alzheimer s disease patients, which leads to the question if prions are related to that disease. Although it has not been proven yet, the hypothesis is quite reliable.

Can prions infectivity be reduced or eliminated?

There were some experiments done with substances to see if prion infectivity could be reduced or eliminated. One of the substances used was protease, which has only effects on proteins. Protease reduced prion infectivity indeed, but was not totally effective. Thats why PrPc is known to be protease sensitive and PrPsc is relatively resistant to proteases (thats one difference).

Also by boiling a prion solution in sodium dodecyl sulfate (SDS) the infectivity was reduced as the protein was denatured. Finally, extremely high doses of radiation inactivated the scrapie agent but this was not a good solution.

How do Prions infect?

There is a theory proposed by the scientists of the National Institute of Allergy and Infectious Diseases ( NIAID ) which states that prions do not need DNA but that they are simply proteins that convert other proteins to their cause. The experiment consisted in adding a traceable radioactive particle to a certain protein that was introduced in unlabeled scrapie and after a few days of incubation an enzyme was added to the solution in order to get rid of any protein left other than prions, the result was that they found a prion with the radioactive trace. Therefore we can say that the protein was transformed by the prion. The suggested theory is that prions form a sort of wall, where this harmless protein fits exactly like a brick and by the yet unknown how change of only one amino acid and turning the alpha-helix protein into a beta-plated one. This helps the prions as beta-pleated shaped proteins tend to be stickier ( because of the charges involved in the hydrogen bonds ).

Bovine Spongiform Encephalopathy (BSE) or Mad Cow disease

This prion infection has gained popularity again in the news headlines when it was discovered by the press. Before it had been known to scientists since the early 1980+s. The unusual popularity gained by this disease was because, eventhough yet not scientifically proved, that it could be transmitted to humans. This could either be by ingesting beef steaks or drinking cow+s milk. What is scientifically proved is the fact that it can be transmitted to cats, mice and other ruminants by the ingestion of the infected cow parts, especially the brain, which is a major point of infection as the PrP protein, which is supposed to be the one infected or rather mutated, is related to the nervous system to be exact with synapses. Eventhough other prion diseases such as Kuru are transmitted by brain ingestion, Kuru is a disease unique for humans while BSE is related only, until now, to other animals. Other prion diseases related to other animals are Scrapie, which attacks sheep, Transmissible Mink Encephalopaty, which att

acks mink and Chronic Wasting Disease which attacks elks and muledeers.

It is known that BSE was adquired by British cows when they started consuming a prepared industrial food which was made with what was left of sheep bones and meat, most of these had been infected by scrapie. This prion is known to survive pasteurization and all cooking methods such as frying and stewing. Yet there are no certain ways on how to treat prion diseases and the only way to avoid more infection is by killing the animals and get totally rid of their bodies as prions can survive in placenta and stay on the ground for a long time and also in the meat. It is not enough to get rid of the mother as the disease is hereditary.

Human prion diseases

CJD (Creutzfeld-Jacob Disease- It occurs most frequently in children and adult women,who suffer involuntary trembling and jerking (ataxia) of the leg muscles, incoordination then spreading to the arms, slurred speech, incontinence,and finally they are incapable of making sounds or swallowing).

*Today human growth hormone is manufactured through biotechnology engineering (r-hGH) so transmission of the Creutzfeldt-Jakob prion is no longer a risk with these recombinant products.

GSS (Gerstmann-Straussler-Scheinker Syndrome).

FFI (Fatal Familial Insomnia).

Kuru.( laughing death)

Alpers Syndrome.

* Sporadic CJD is about 1 per million per year.

GSS is less sporadic as it occurs in only 2% the times CJD occurs.

1 out of 10,000 people are believed to be infected with CJD at the time of their

death.

Other yet diseases to be proved are Alzheimer Disease (disease in which amyloid plaques when increased, rises mental disfunction. Amyloids explained above), Parkinson, amytrophic lateral sclerosis and other mental diseases which arrise with age.

Sporadic CJD is about 1 per million per year.

GSS is less sporadic as it occurs in only 2% the times CJD occurs.

1 out of 10,000 people are believed to be infected with CJD at the time of their death.

Prion diseases in humans usualy are related to senile people as they usually appear after the age of 40 as it is known that prions take some time to act on the human body, unlike hamsters which develop the disease rapidly. These are related to loss of motor control, dementia and paralysis wasting. The disease leads eventually to death after an attack of pneumonia usually. This symptoms are present because of the attack the Central Nervous System (CNS) recieves by the prions. As it was said earlier, the believed protein PrP which mutates to become a prion disease, is closely related to synapses which are the connectors of the human nervous system. Therefore the mutation of the protein may cause disorders in the transmission of the electrical impulses and as it usually happens in old people the replacement of this protein takes very long or it does not take place. When the dead people are opened the brain presents particular symptoms such as non-inflamatory lesions, vacuoles, amyloid protein deposits, astroglios

is and gives a spongy appearence to the brain tissue. Most of these diseases are hereditary but some as CJD are known to appear esporadically.

What exactly are prions, we still don t know, but as knew methods are used for research things appear clearer. Some solutions have appeared for prions, like the hormone manufactured through biotechnology engineering (r-hGH) that stops the transmission of the Creutzfeldt-Jakob prion, but many other diseases may be cured in the future, including Alzheimer s disease, which affects a great part of population, if it is related to it. As Stanly B. Prusiner said:

If the prion is indeed a single protein and the product of a gene native to the host organism, the time may have come for a reconsideration of what is meant by the concept of infection.