a lecture that describes what are prions, what diseases they cause, and how they cause disease, incubation period and symptoms and signs of the disease they cause.
2. What are prions
• A prion is a misfolded protein that can induce misfolding of
normal variants of the same protein and trigger cellular death.
3. • Prions cause prion diseases known as transmissible spongiform
encephalopathies (TSEs) that are transmissible,
fatal neurodegenerative diseases in humans and animals.
• Prion isoforms of the major prion protein (PrP), whose specific
function is uncertain, are hypothesized as the cause of
transmissible spongiform encephalopathies (TSEs).[8] These
include scrapie in sheep, chronic wasting disease (CWD) in
deer, bovine spongiform encephalopathy (BSE) in cattle
(commonly known as "mad cow disease") and Creutzfeldt–
Jakob disease (CJD) in humans.
4. pathogenesis
• All known prion diseases in mammals affect the structure of
the brain or other neural tissue; all are progressive, have no known
effective treatment, and are always fatal.
• Prions are a type of intrinsically disordered protein, which
continuously change their conformation unless they are bound to a
specific partner such as another protein.
• With a prion, two protein chains are stabilized if one binds to another
in the same conformation. The probability of this happening is low,
but once it does, the combination of the two is very stable.
• Then more units can get added, making a sort of "fibril".
• Prions form abnormal aggregates of proteins called amyloids, which
accumulate in infected tissue and are associated with tissue damage
and cell death.
5. Structure
• The major prion protein (PrP) that prions are made of is found
throughout the body, even in healthy people and animals.
However, PrP found in infectious material has a
different structure and is resistant to proteases, the enzymes in
the body that can normally break down proteins. The normal
form of the protein is called PrPC, while the infectious form is
called PrPSc
• The infectious isoform of PrP, known as PrPSc, is able to convert
normal PrPC proteins into the infectious isoform by changing
their conformation, or shape; this, in turn, alters the way the
proteins interconnect. PrPSc always causes prion disease.
6.
7.
8. Other TSEs include:
• Creutzfeldt-Jakob disease and fatal familial insomnia in humans
• Bovine spongiform encephalopathy in cattle (also known as "mad cow"
disease)
• Scrapie in sheep and goats
• Chronic wasting disease in deer and elk
9. kuru
• Kuru is a rare and fatal brain disorder that occurred at
epidemic levels from the 1950s to 1960s among the Fore
people in the highlands of New Guinea. The disease was
the result of the practice of ritualistic cannibalism among
the Fore, in which relatives prepared and consumed the
tissues (including brain) of deceased family members.
Brain tissue from individuals with kuru was highly
infectious, and the disease was transmitted either
through eating or by contact with open sores or wounds.
10. Incubation period and clinical picture
• Similar to other the TSEs, kuru has a long incubation period; it was years or
even decades before an infected person showed symptoms. Because kuru
mainly affected the cerebellum, which is responsible for coordination, the first
symptoms were usually an unsteady gait, tremors, and slurred speech. Unlike
most of the other TSEs, dementia was either minimal or absent. Mood
changes were often present. Eventually, individuals became unable to stand
or eat, and they died in a comatose state from six to 12 months after the first
appearance of symptoms.
11. Creutzfeldt-Jakob disease
• Creutzfeldt-Jakob disease (CJD) is a rare, rapidly
worsening brain disorder that causes unique changes in
brain tissue and affects muscle coordination thinking, and
memory. There are about 350 cases per year in the U.S.
12. There are three major categories of CJD
1.Sporadic CJD—The disease develops in someone when the cause is unknown.
This accounts for at least 85 percent of cases.
2.Hereditary CJD—There may be a known gene mutation that occurs in a family.
About 10 to 15 percent of cases of CJD in the United States are hereditary.
3.Acquired CJD—Rarely, the disease is transmitted by exposure to brain or nervous
system tissue, usually through certain medical procedures such as surgical grafts of
dura mater (a tissue that covers the brain), transplanted corneas, and implantation
of inadequately sterilized electrodes in the brain. Doctors call these iatrogenic
cases. Fewer than one percent of cases have been acquired CJD.
13. The two main symptoms of CJD are:
1.Severe mental deterioration and dementia
2.Involuntary (unwanted) muscle jerks (myoclonus) or muscle movement
• A type of CJD called variant CJD (or vCJD) can be acquired by eating meat
from cattle affected by a disease similar to CJD called bovine spongiform
encephalopathy (BSE, or “mad cow” disease). Variant CJD begins primarily
with psychiatric symptoms, affects younger people than other types of CJD,
and has a longer than usual duration from onset of symptoms to death.
14. Early symptoms of the disease may include:
• Lack of coordination
• Problems with walking and balance
• Impaired thinking, memory, and judgment
• Behavior changes
• Depression, mood swings, and anxiety
• Confusion
• Insomnia or changes in sleeping patterns
• Unusual sensations
• Changes in vision
15. As CJD progresses, symptoms may include:
• Weakness of the arms and legs
• Blindness
• Loss of ability to move or speak
• Pneumonia and other infections
• Coma
16. Diagnosis
• Electroencephalography (EEG)—This test records the brain's electrical pattern and find a specific type of
abnormality in major types of CJD.
• Cerebrospinal fluid-based tests—This testing looks for the 14-3-3 protein (a marker for some prion diseases,
such as CJD) to detect the abnormal prion protein in the fluid that surrounds the brain and spinal cord.
• Magnetic resonance imaging (MRI)—This type of brain imaging is accurate in about 90 percent of cases.
• The only way to confirm a diagnosis of CJD is by brain biopsy or an autopsy. In a brain biopsy, a
neurosurgeon removes a small piece of tissue from the living person's brain so it can be examined by a
neuropathologist. This procedure may be dangerous for the individual and is generally discouraged unless it
is needed to rule out a treatable disorder. In an autopsy, the whole brain is examined after death.
17. Sterilization of prions
• After the device is clean, it should be sterilized either steam sterilization
with an autoclave, or a combination sodium hydroxide and autoclaving,
using one of the four following methods:
• Option 1. Autoclave at 134°C for 18 minutes in a prevacuum sterilizer.
• Option 2. Autoclave at 132°C for 1 hour in a gravity displacement sterilizer.
• Option 3. Immerse in 1 N NaOH (1 N NaOH is a solution of 40 g NaOH in 1 L water)
1 hour; remove and rinse in water, then transfer to an open pan and autoclave
(121°C gravity displacement sterilizer or 134°C porous prevacuum sterilizer) for 1
hour.
• Option 4. Immerse in 1 N NaOH for 1 hour and heat in a gravity displacement
sterilizer at 121°C for 30 minutes, then clean and subject to routine sterilization.
