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.