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Essay/Term paper: Prions

Essay, term paper, research paper:  Chemistry

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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.

 

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