Detailed notes on Prion diseases written by Muhammad Naseem

1. Prion diseases
Prion diseases, also known as transmissible spongiform encephalopathies (TSE's) are a group
of progressive neurodegenerative conditions. These illnesses exist in both animals and
humans. Scrapie, a disease affecting sheep and goats, was the first prion disease to be
identified in the 1730s.
OR
A prion is a type of protein that can trigger normal proteins in the brain to fold abnormally. Prion
diseases can affect both humans and animals and are sometimes spread to humans by
infected meat products. The most common form of prion disease that affects humans is
Creutzfeldt-Jakob disease (CJD).
Causes:
Prion diseases are caused by misfolded forms of the prion protein, also known as PrP. These
diseases affect a lot of different mammals in addition to humans – for instance, there is scrapie
in sheep, mad cow disease in cows, and chronic wasting disease in deer.
Classification:
In the early 1980s American neurologist Stanley B. Prusiner and colleagues identified the
“proteinaceous infectious particle,” a name that was shortened to “prion” (pronounced “pree-
on”). Prions can enter the brain through infection, or they can arise from mutations in the gene
that encodes the protein. Once present in the brain prions multiply by inducing benign proteins
to refold into the abnormal shape. This mechanism is not fully understood, but another protein
normally found in the body may also be involved. The normal protein structure is thought to
consist of a number of flexible coils called alpha helices. In the prion protein some of these
helices are stretched into flat structures called beta strands. The normal protein conformation
can be degraded rather easily by cellular enzymes called proteases, but the prion protein
shape is more resistant to this enzymatic activity. Thus, as prion proteins multiply, they are not
broken down by proteases and instead accumulate within neurons, destroying them.
Progressive neuron destruction eventually causes brain tissue to become filled with holes in a
sponge like, or spongiform, pattern.
Examples:
Creutzfeldt-Jakob Disease CJD humans
variant Creutzfeldt-Jakob
Disease
vCJD humans; acquired from cattle with BSE
Bovine Spongiform
Encephalopathy
BSE "mad cow disease"

2. Kuru
infectious; in humans who practiced cannibalism in
Papua New Guinea
Gerstmann-Sträussler-Scheinker
disease
GSS inherited disease of humans
Fatal Familial Insomnia FFI inherited disease of humans
Scrapie infectious disease of sheep and goats
other animal TSEs cats, mink, elk, mule deer
Prion Protein Cellular:
The normal protein
 It is called PrPC
(for cellular).
 It is a glycoprotein normally anchored to the surface of cells.
 It has its secondary structure dominated by alpha helices (probably 3 of them).
 It is easily soluble.
 It is easily digested by proteases.
 It is encoded by a gene designated (in humans) PRNP located on our chromosome 20.
Prion Protein Scrapie:
The abnormal, disease-producing protein
 It is called PrPSc
(for scrapie).
 It has the same amino acid sequence as the normal protein; that is, their primary
structures are identical but its secondary structure is dominated by beta
conformation.
 It is insoluble in all but the strongest solvents.
 It is highly resistant to digestion by proteases.
 When PrPSc
comes in contact with PrPC
, it converts the PrPC
into more of itself (even in
the test tube).
 These molecules bind to each other forming aggregates.
 It is not yet clear if these aggregates are themselves the cause of the cell damage or are
simply a side effect of the underlying disease process.
Inherited Prion Diseases:
1. Creutzfeldt-Jakob disease (CJD):
It is a rare, degenerative, invariably fatal brain disorder. It
affects about one person in every one million people per year worldwide; in the United
States there are about 300 cases per year. CJD usually appears in later life and runs a
rapid course. Typically, onset of symptoms occurs about age 60, and about 90 percent
of individuals die within 1 year. In the early stages of disease, people may have failing
memory, behavioral changes, lack of coordination and visual disturbances. As the illness

3. progresses, mental deterioration becomes pronounced and involuntary
movements, blindness, weakness of extremities, and coma may occur.
2. Erstmann–Sträussler–Scheinker syndrome (GSS):
It is a very rare, usually familial, fatal neurodegenerative disease that
affects patients from 20 to 60 years in age. It is also in a group of hereditary prion
protein diseases or also known as TSEs.
3. Fatal Familial Insomnia (FFI):
Fatal insomnia is a rare prion disease that interferes with sleep and leads
to deterioration of mental function and loss of coordination. Death occurs within a few
months to a few years. Fatal insomnia has two forms: Familial: This form, called fatal
familial insomnia, is inherited.
Infectious Prion Diseases:
1) Kuru:
Kuru is a very rare disease. It is caused by an infectious protein (prion) found in
contaminated human brain tissue. Kuru causes brain and nervous system changes
similar to Creutzfeldt-Jakob disease. Similar diseases appear in cows as bovine
spongiform encephalopathy (BSE), also called mad cow disease.
Symptoms of Kuru include:
 Arm and leg pain.
 Coordination problems that become severe.
 Difficulty walking.
 Headache.
 Swallowing difficulty.
 Tremors and muscle jerk.
2) Scrapie:
Scrapie is a fatal, degenerative disease that affects the nervous systems of
sheep and goats. Like other spongiform encephalopathies, the cause of scrapie is
unknown, but is thought to be caused by an infectious misfolded protein called a prion.
Symptoms of scrapie: Signs of scrapie vary widely among individual animals and develop
very slowly. Due to damage to nerve cells, affected animals usually show behavioral
changes, tremor (especially of head and neck), pruritus, and locomotors incoordination that
progresses to recumbency and death.

4. Miscellaneous Infectious Prion Diseases:
A number of TSEs have been found in other animals.
 Cats are susceptible to Feline Spongiform Encephalopathy (FSE)
 Mink are also susceptible to a TSE.
 Even though mad cow disease has not been seen in North America, a similar disease
called chronic wasting disease which is found in elk and mule deer in the Rocky
Mountains of the U.S.
Sporadic Prion Diseases:
Appearing or happening of the same things at irregular intervals in time;
occasional: sporadic renewals of enthusiasm. Appearing in scattered or isolated instances, as
a disease.
The sporadic form of prion disease is by far the most common. It’s often estimated that human
prion disease cases are 85% sporadic, 15% genetic and < 1% acquired.

5. Written byMuhammad Naseem
StudentofBSMicrobiology1ST
Semester