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General Background
on Prions
Introduction to Prions
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Pronounced “pree-on”
Shortened term for:
Proteinaceous Infections Particle
Causes TSE (Transmissible Spongiform
Disease) which attacks the central nervous
system (the brain).
Discovery
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Study started in 1967 by British scientist,
Tikvah Alper, at Hammersmith Hospital in
London.
Discovered by American neurologist,
Stanley B. Prusiner, in 1982.
Where are prions?
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Proteins on the cell membrane of neurons
of the brain in mammals
Normal prion protein is noted as PrPC
Mutated prion protein is noted as PrPSC
The secondary structure of the prion
protein seems to be affected.
Basic Structure

Normal prions contain
about 200-250 amino
acids twisted into three
telephone chord-like coils
known as helices, with
tails of more amino acids.
Basic Structure


Normal prions contain
about 200-250 amino
acids twisted into three
telephone chord-like coils
known as helices, with
tails of more amino acids.
The mutated, and
infectious, form is built
from the same amino
acids but take a different
shape.
Normal
Mutated
Basic Structure


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Normal prions contain
about 200-250 amino
acids twisted into three
telephone chord-like coils
known as helices, with
tails of more amino acids.
The mutated, and
infectious, form is built
from the same amino
acids but take a different
shape.
100 times smaller than
the smallest known virus.
Normal
Mutated
Basic Structure
Normal
Mutated
Differences From Bactera & Viruses

Prions do not contain nucleic acid; they
don’t have DNA or RNA.
Differences From Bactera & Viruses
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Prions do not contain nucleic acid; they
don’t have DNA or RNA.
They are extremely resistant to heat and
chemicals.
Differences From Bactera & Viruses
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Prions do not contain nucleic acid; they
don’t have DNA or RNA.
They are extremely resistant to heat and
chemicals.
Prions are very difficult to decompose
biologically; they survive in soil for many
years.
Prion Diseases
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Humans:
CJD (Creutzfeldt Jakob Disease)
GSS (Gerstmann Straussler Syndrome)
Symptoms of prion disease in
humans
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Rapidly developing dementia
Difficulty walking and changes in gait
Hallucinations
Muscle stiffness
Confusion
Fatigue
Difficulty speaking
How Prion disease is diagnosed
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MRI scans of the brain
Samples of fluid from the spinal cord
(spinal tap)
Electroencephalogram, which analyzes
brain waves; this painless test requires
placing electrodes on the scalp
Blood tests
Neurologic and visual examinations to
evaluate for nerve damage and vision loss
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Neurodegenerative disease experts have long been
concerned that prion diseases might be transmitted
through the transfusion of blood products.
Although cross-species transmission between cows and
humans of the disease is relatively difficult, inter-species
transmission between humans through blood transfusion
is efficient and if unmanaged, could pose a serious risk.
This is particularly worrying since prion diseases typically
have very long silent incubation periods, sometimes
extending over many decades, and at present there is no
reliable blood test to screen for the presence of the
infectious prion agent.
Lancet paper: vCJD case report
14 December 2006
Prevention of Prion disease on
humans
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Properly sterilizing medical equipment may
prevent the spread of the disease. If you
have or may have CJD, you should not
donate organs or tissue, including corneal
tissue. Newer regulations that govern the
handling and feeding of cows may help
prevent the spread of prion diseases.
Prion Diseases
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Humans:
CJD (Creutzfeldt Jakob Disease)
GSS (Gerstmann Straussler Syndrome)
Cattle:
BSE (Bovine Spongiform Encephalopathy, better known
as Mad Cow Disease)
Prion Diseases
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Humans:
CJD (Creutzfeldt Jakob Disease)
GSS (Gerstmann Straussler Syndrome)
Cattle:
BSE (Bovine Spongiform Encephalopathy, better known
as Mad Cow Disease)
Sheep:
Scrapie
Deer/Elk:
CDW (Chronic Wasting Disease)
Figure 1. Histopathology showing spongiform degeneration and astrocytic gliosis (adapted from the Prion Group at the University of Duesseldorf )
Vaccine?
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The development of a vaccine against the
infectious form of prions has proven to be
unsuccessful due to the lack of innate or
antigen-induced immune response against
the host-encoded protein.
Controversy
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DNA and RNA are the only substances now
known to replicate in body tissues, so how do
prions make copies of themselves without any
nucleic acids?
Controversy
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DNA and RNA are the only substances now
known to replicate in body tissues, so how do
prions make copies of themselves without any
nucleic acids?
Some believe TSEs are caused by an
unidentified slow-acting virus.
Others believe a small virus accompanies a prion
and they work together to cause disease.
One proposed method for prion
replication
Note that normal PrPC is onvolved in replication of mutated PrPSc
References
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www.hartnell.cc.ca.us/faculty/jhodin/Group9.ppt
http://www.scq.ubc.ca/prions-infectious-proteins-repsonsiblefor-mad-cow-disease/
http://www.hopkinsmedicine.org/healthlibrary/conditions/nervo
us_system_disorders/prion_diseases_134,56/
http://prion.systemsbiology.net/page/PosterView/display/poster
_id/13
http://www.ucl.ac.uk/news/news-articles/0612/06121401