Assignment on Prions
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Transcript of Assignment on Prions
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Prions contain no genome but still they canreplicate and destroy their host. Like the
other pathogens, they are not a prokaryotic
organism or even a eukaryotic organism.They are the smallest and simplest
infectious agents and they cause a number
of neurodegenerative diseases in mammals.
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Prion is a microscopic, infectious form of a
protein molecule that does not contain a DNA orRNA, that is, it lacks genetic material.
Mammals produce the normal protein as part of
normal cell development, but during infection,misfolded proteins can convert normal host prion
protein into a toxic, misfolded form. When this
happens enough times, massive tissue and celldamage can occur. Infectious prions are linked to
a number of fatal and untreatable diseases in
humans and other animals.
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PrP is known as the major prior protein. PrP
has two isomers having symmetrical spatial
arrangement and are found in the nervoussystem. These are PrPC and PrPSc. PrPC is the
normal cellular protein and PrPSc is the
abnormal protein. This PrP
Sc
is theproteinaceous infectious particle or prion.
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In humans, PrPCcontains 42% alpha-helix and
3% beta-structure. It is rich in alpha-helix. Itsnormal cellular function is still unknown. On
the other hand, PrPSccontains 30% alpha-helix
and 43% beta-structure. PrPSchas a higherproportion of -sheet structure than -helix
structure. Its exact 3D structure is not known.
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The PrPScare fibrous proteins and cannot be
broken down by protease enzyme. Due to these
factors and their insoluble nature, these diseasedprion proteins build up in the brain and form
clusters, creating holes in the brain tissues and
ultimately killing the cells. The areas of the
brain containing the dead cells start to look
spongy in appearance. Prion diseases are called
transmissible spongiform encephalopathies or
TSEs.
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People who inherit prion diseases are due to PRNP
mutations (Castilla et al., 2004).
Fig:Showing hereditary prion disease developed due to
PRNP gene mutations in a person's DNA.
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In the 1700s the first TSEs, scrapie,
appeared in Great Britain.
In the 1920s the first case of a
progressive neurological disturbance was
discovered in humans by the neurologists
Hans Creutzfeldt and Alfons Jacob.
In the 1950s Kuru was discovered.
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In the 1980s, 60 people died from CJD
after being infected by contaminated
surgical instruments and 85 people diedafter receiving growth hormone
injections, infected with prion.
In 1985, experiments were done to
demonstrate that a normal form of PrP
was produced by uninfected people.
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Prion diseases are caused by proteins they cannot
be treated by antibiotics or antiviral.
PrPScis extremely heat resistant and temperature
greater than 130C for 30 to 60 minutes is needed
for inactivation. For this reason autoclaving willnot destroy prions. It remains unaffected after
exposure to radiation, strong acids and non-polar
organic solvents.PrPSc is resistant to the enzyme, proteinase K.
For this reason PrPSc can accumulate in the brain
and creates a sponge-like appearance of the brain.
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TSEs diseases are:
In humans
Creutzfeldt-Jakob Disease (CJD)
variant Creutzfeldt-Jakob Disease (vCJD)
Kuru
Gerstmann-Strussler-Scheinker disease (GSS
Fatal Familial Insomnia (FFI).
In animals
Bovine Spongiform Encephalopathy (BSE)
Chronic wasting disease (CWD)
Scrapie
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Prions do not transmit through air, through
touching or through other manners of normalcontact. They can be transmitted through
contact with infected tissues, body fluids, or
contaminated medical instruments.Human prion diseases can occur due to
sporadic, hereditary or infectious cause or
through accidental transmission throughmedical procedures, known as iatrogenic.
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PRNP gene mutations cause CJD, GSS and FFI.
CJD causing prions are transmitted in iatrogenic
manner with corneal transplants. vCJD occurs in humans due to eating beef
products, obtained from affected cattle.
Kuru is transmitted from an affected human to ahealthy human.
Scrapie occurs as infection in genetically
susceptible sheep and goats.
BSE is also known as "Mad Cow Disease" and is
seen to occur in cattle.
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In Humans
neurological and psychological symptoms are:1) Insomnia and/or hallucination
2) Spongy appearance in the cross-section of thebrain
3) Loss of memory
4) Seizures
physical symptoms are:
1) Weight loss
2) Ataxia
3) Tremors
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In Animals
Scrapie produces an itching sensation,
strange gaits and convulsive collapse. In BSE unrestrained digging of holes is
seen.
For CWD (chronic wasting disease)
gradual weight loss, fewer interactions
with other animals, lack of energy,
lowering of the head, blank face are
commonly seen.
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Yeast prions have the same behavior as PrP
and are usually non toxic to their hosts.Researches were done on fungal prions and
this helped to get the idea about prion
domains. Prion domains are locations in aprotein which promote the conversion of
prion state.
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Fungal PrionsProtein Natural
host
Normal
function
Prion
state
Prion
phenotype
Year
identified
Ure2p S.
cerevisia
e
Nitrogen
catabolite
repressor
[URE3] Growth on
poor nitrogen
sources
1994
Cyc8 S.
cerevisia
e
Transcriptiona
l repressor
[OCT+
]
Transcriptiona
l derepression
of multiple
genes
2009
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Prion disease cannot stimulate immunity.
Vaccines have no function in TSEs.
In humans prion diseases occur easily
through transplantation of prion affected
tissue or by eating of beef from affectedanimals.
Only diagnosis of prion disease is by
examining the brain after the death of the
mammal.
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Prion diseases, such as BSE and CJD have
a very long incubation period of months to
decades. Although the conversion of PrPCto PrPSc
has already begun still there will be no
visible symptoms for a long time. So thereis no efficient treatment for prion diseases.
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Surround Optical Fiber Immunoassay or
SOFIA (Rubenstein, 2011).
Antiprion antibodies (Jones et al., 2010).
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After 20 years of research scientists have
discovered PrPChelp to maintain the myelin
sheath that protects the nerves of the body.
They activate myelin repairmen(Abbott,2010). Still a lot of researches are being on
prions in order to find an effective and
efficient cure for prion diseases.