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• Prions
• Prions, also known as the agents of transmissible spongiform encephalopathies
(TSE),
• Causes diseases of humans: Kuru, Creutzfeldt-Jakob
disease, Gerstmann- Sträussler-Scheinker syndrome, and fatal familial insomnia.
• Several diseases of animals: Scrapie of sheep and goats, bovine spongiform
encephalopathy, feline transmissible encephalopathy, transmissible mink
encephalopathy, and chronic wasting disease of deer and elk.
• In each of these diseases the common lesion is a spongiform degeneration of the
gray matter of the brain with astroglial hypertrophy and proliferation.
• These uniformly fatal diseases are caused by prions, that is “infectious proteins,
lacking a nucleic acid genome.” The name prion is an acronym from proteinaceous
infectious particle.
Tribble-like amyloid plaques of variant Creutzfeldt-Jakob Disease acquired from
eating prion-infected beef.
https://biol342-s19.community.uaf.edu/tag/transmissiblemink-encephalopathy/
https://www.sciencedirect.com/topics/bioche
mistry-genetics-and-molecular-biology/scrapi
• Prions
The etiology of this group of diseases posed an extraordinary
biological enigma for many years, because it was understood that:
1. Disease can be transmitted by tissues and tissue extracts in a
similar way to conventional infections.
2. Disease can also arise spontaneously, or as an inherited disorder.
3. Infectious inocula had been shown to lack nucleic acid, the
physical basis for encoding all biological information in all living
organisms and viruses.
• Stanley Prusiner was awarded the 1997 Nobel Prize in Physiology
or Medicine for his discovery of the nature of prions and the
exceptional mechanisms of prion pathogenesis.
• He named it as “ protein and infection, hence prion
• Classification
• Prions have not been classified in the same
way as viruses, thus there are no families,
genera, or species.
• They first are identified by their host
species, clinical disease, and their associated
lesions.
• Properties
• Prions are normal cellular proteins that have undergone a
certain conformational change as a result of posttranslational processing
of a normal cellular protein and
thereby have become pathogenic.
• The normal human prion protein, PrPC, is composed of 208
amino acids. It is encoded in the genome of most mammals
and expressed in many tissues, especially in neurons and
lymphoreticular cells.
• PrPC in anti-apoptotic activities, cell signalling and adhesion,
synaptic function, and protection against oxidative stress
• The amino acid sequence of PrPC and the abnormal isoform
of the protein, PrPSc in a given host are identical.
• Only the conformation is changed in the PrPSc isoform, from
a structure made up predominantly of α-helices to one made
up predominantly of β-sheets
• Re-Folding of Normal Prion Is Triggered by Rogue
Prion
Normal prions can be induced to change their
conformation by contact with a misfolded prion. When
the pathological improperly folded form PrPsc comes
in contact with the normal prion, PrPc, the normal
protein changes into the abnormal form.
• The alternate conformation has a tendency to
aggregate, forming clumps that damage nerve cells.
• Human Prion diseases
Bovine Spongiform Encephalopathy (BSE)
• Bovine spongiform encephalopathy (BSE) was
first detected in cattle in 1986 in the United
Kingdom;
• It was called “mad cow disease” in the popular
press.
• Spread to humans is believed to result in
variant Creutzfeldt–Jakob disease (vCJD)
• Transmitted to human by eating contaminated
food.
• Creutzfeldt-Jakob Disease
• It is a degenerative brain disorder that leads to dementia and,
ultimately, death.
• The majority of prion disease cases in humans are sporadic CJD, which
has a worldwide incidence of 1 to 2 cases per million population per year.
• Around 5–10% of CJD cases are associated with a family history or
evidence of a PRNP gene mutation, indicating a genetic basis.
• Kuru
• It is a fatal neurological disease,
• Occurred only in the Fore tribe in the New Guinea highlands where
ritualistic cannibalism was practiced on deceased relatives.
Gerstmann-Sträussler-Scheinker Syndrome and Fatal Familial Insomnia
• Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia
are very rare familial diseases caused by autosomal dominant mutations
in the PRNP gene.
• Diagnosis
• A diagnosis of CJD is confirmed by demonstration in
the brain tissue of typical neuropathological features,
• The presence of protease-resistant PrP on Western
blot,
• or PrPSc by immunohistochemistry,
• or the detection of scrapie-associated fibrils by
electron microscopy.
• This alters the expression of the mRNA. In the case of the viroid,
expression is abnormal and disease results.