Protein

2. In the 1950s, a district medical
officer working in the highlands
of New Guinea observed a fatal
disease among the people of the
Fore (FOR-ay) tribe. The Fore
people called this sickness kuru,
which means "trembling in fear."
After intially becoming unable to
walk, victims of kuru lost the
ability to swallow or chew. Drastic
weight loss would inevitably lead
to death. Today we know that
kuru is one of several diseases in
humans and animals caused by
prion (PREE-on) proteins.
The Mystery of Kuru

3. Introduction to Prions
- Pronounced “pree-on”
- Shortened term for:
Proteinaceous Infections Particle
- Causes TSE (Transmissible Spongiform Disease)
which attacks the central nervous system (the
brain).

4. 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.

5. Basic Structure
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

6. Basic Structure
Normal Mutated

7. Differences From Bacteria &
Viruses
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.

9. Prions (PREE-ons) are
proteins that are unique
in their ability to
reproduce on their own
and become infectious.
They can occur in two
forms called PrP-sen and
PrP-res.

11. Both PrP-sen and PrP-res are made up of the exact
same string of amino acids, the building blocks that
make up proteins. However, the two forms have
different shapes.
PrP-sen is produced by normal healthy cells. The sen
stands for “sensitive” because this version of the
protein is sensitive to being broken down.
PrP-sen is present mainly in neurons in the brain, but
is also found in other cell types.

12. Scientists don’t know the exact function of PrP-sen,
but there is evidence that it may be involved in
communication between neurons, cell death, and
controlling sleep patterns. Interestingly, mice that are
genetically engineered to produce no PrP-sen seem to
be healthy.
The second type of prion protein, known as PrP-res, is
the disease-causing form. Organisms with it develop
spongiform disease. “res” stands for “resistant” because
this version of PrP is resistant to being broken down.

13. Unlike other infectious agents, prions do not contain
genetic material. However, once they infect an
individual, prions can replicate. How is this possible?
Scientists are still working out the details, but evidence
supports the idea that when PrP-sen comes into
contact with PrP-res it is converted to PrP-res. The
result is a chain reaction that multiplies copy after
copy of the infectious prion.
Because of their abnormal shape, PrP-res proteins
tend to stick to each other. Over time, the PrP-res
molecules stack up to form long chains called
“amyloid fibers”.

14. Amyloid fibers are toxic to cells, and ultimately kill
them.
Cells called astrocytes crawl through the brain
digesting the dead neurons, leaving holes where
neurons used to be. The amyloid fibers remain.

18. The History of
Prions:
1730s
Earliest written
record of
Scrapie in
English sheep;
already
prevalent in
central
Europe.

19. 1950s
High levels of kuru
appear among the Fore
people of New Guinea.
1960s
Scientists
experimentally transmit
Kuru and CJD to
chimpanzees,
demonstrating the
transmissible nature of
these diseases.

20. 1980s
60 people die from
CJD after being
infected by
contaminated
surgical
instruments. 85
people die after
receiving prion-
infected growth
hormone injections.

21. 1982
Dr. Stanley Prusiner
coins the term
"prion"
(PROteinaceous
INfectious particle).
Highly purified
PrP-res is shown to
be infectious. He
goes on to win the
Nobel Prize in
Medicine in 1997.

22. 1985
Scientists identify
the PrP gene and
discover that
uninfected people
produce a normal
form of the PrP
protein.

23. 1986
By the year 2000,
nearly 180,000 cattle
will become
infected. To stop the
spread, thousands
of cattle are killed.

24. A Survey of Spongiform Diseases

25. Classic CJD or Creutzfeldt-Jakob disease (human)
The most prevalent of the spongiform diseases
Occurs spontaneously in 1 out of a million people
10% of cases are inherited mutations in the PRPN gene
Usually strikes people age 50 to 75
Symptoms: dementia, muscle twitching, vision
problems
Fatal Familial Insomnia (human)
All cases are inherited mutations in the PrP
gene
Usually strikes people age 36 to 61
Disruption of sleep/wake cycle leads to
coma, then death
Scrapie (goats, sheep)
Occurs as infection in genetically susceptible
sheep
There is no evidence of spread to humans

26. BSE or Bovine Spongiform
Encephalopathy (cattle)
Also known as "Mad Cow Disease" because
infected animals act strangely and can be
aggressive
Spread rapidly through Britain by rendering
Chronic Wasting Disease (deer, elk)
Infectious disease in wild deer and elk
primarily in the western United States
Drooling, difficulty swallowing, weight loss
Kuru (human)
Struck members of the Fore tribe in the
1950s and 1960s
Muscle weakness, loss of coordination,
tremors, inappropriate episodes of laughter
or crying
Transmitted by ritual cannibalism as part of
funeral ceremonies

28. Controversy
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.