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Assignment On Prions

Prions are infectious proteins that cause neurodegenerative diseases in mammals by converting normal prion proteins (PrPC) into abnormal, misfolded proteins (PrPSc) which accumulate in the brain, damaging tissue and cells. Prions lack nucleic acids and can withstand heat, radiation, and chemical disinfection. Prion diseases like Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy ("mad cow disease") in cattle have long incubation periods and are untreatable, making prions a serious public health concern.

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684 views

Assignment On Prions

Prions are infectious proteins that cause neurodegenerative diseases in mammals by converting normal prion proteins (PrPC) into abnormal, misfolded proteins (PrPSc) which accumulate in the brain, damaging tissue and cells. Prions lack nucleic acids and can withstand heat, radiation, and chemical disinfection. Prion diseases like Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy ("mad cow disease") in cattle have long incubation periods and are untreatable, making prions a serious public health concern.

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Rinta Moon
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Prions contain no genome but still they can replicate 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.

Prion is a microscopic, infectious form of a protein molecule that does not contain a DNA or RNA, 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 cell damage can occur. Infectious prions are linked to a number of fatal and untreatable diseases in humans and other animals.

PrP is known as the major prior protein. PrP has two isomers having symmetrical spatial arrangement and are found in the nervous system. These are PrPC and PrPSc. PrPC is the normal cellular protein and PrPSc is the abnormal protein. This PrPSc is the proteinaceous infectious particle or prion.

In humans, PrPC contains 42% alpha-helix and 3% beta-structure. It is rich in alpha-helix. Its normal cellular function is still unknown. On the other hand, PrPSc contains 30% alpha-helix and 43% beta-structure. PrPSc has a higher proportion of -sheet structure than -helix structure. Its exact 3D structure is not known.

The PrPSc are fibrous proteins and cannot be broken down by protease enzyme. Due to these factors and their insoluble nature, these diseased prion 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.

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.

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.

In the 1980s, 60 people died from CJD after being infected by contaminated surgical instruments and 85 people died after 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.

In 1997, Stanley Prusiner won the Nobel Prize in Medicine. In 2000, Mad Cow Disease outbreak infected 180,000 cattle. In 2005 it was made known that from British beef, vCJD is connected to exposure to BSE. By April 2005, 155 U.K. residents were dead due to eating beef of BSE or Mad Cow Disease affected cows.

Prion diseases are caused by proteins they cannot be treated by antibiotics or antiviral. PrPSc is extremely heat resistant and temperature greater than 130C for 30 to 60 minutes is needed for inactivation. For this reason autoclaving will not 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.

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

Prions do not transmit through air, through touching or through other manners of normal contact. 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 through medical procedures, known as iatrogenic.

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 a healthy 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.

In Humans neurological and psychological symptoms are: 1) Insomnia and/or hallucination 2) Spongy appearance in the cross-section of the brain 3) Loss of memory 4) Seizures physical symptoms are: 1) Weight loss 2) Ataxia 3) Tremors

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.

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 a protein which promote the conversion of prion state.

Fungal Prions
Protein

Natural

Normal

Prion

Prion

Year

host
Ure2p

function
Nitrogen

state

phenotype

identified
1994

S.

[URE3] Growth on poor nitrogen

cerevisia catabolite

e
Cyc8

repressor

sources
2009

S.

Transcriptiona [OCT+ Transcriptiona ] l derepression of multiple genes

cerevisia l repressor e

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 affected animals. Only diagnosis of prion disease is by examining the brain after the death of the mammal.

Prion diseases, such as BSE and CJD have a very long incubation period of months to decades. Although the conversion of PrPC to PrPSc has already begun still there will be no visible symptoms for a long time. So there is no efficient treatment for prion diseases.

Surround Optical Fiber Immunoassay or SOFIA (Rubenstein, 2011). Antiprion antibodies (Jones et al., 2010).

After 20 years of research scientists have discovered PrPC help 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.

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