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.
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