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 size 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 attacks 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.