An Introduction OfPrion Proteins

Prepared By:Md. Najmul HossainMBGE,17 BatchUniversity Of Development Alternative

Introduction to Prions

- Pronounced “pree-on”

- Shortened term for:Proteinaceous Infections Particle

- Causes TSE (Transmissible Spongiform Disease) which attacks the central nervous system (the brain).

Basic Structure

The mutated, and infectious, form is built from the same amino acids but take a different shape.

100 times smaller than the smallest known virus.

Normal Mutated

Basic Structure

Normal Mutated

Differences From Bacteria & Viruses

Prions do not contain nucleic acid; they don’t have DNA or RNA.

They are extremely resistant to heat and chemicals.

Prions are very difficult to decompose biologically; they survive in soil for many years.

Prions (PREE-ons) are proteins that are unique in their ability to reproduce on their own and become infectious. They can occur in two forms called PrP-sen and PrP-res.

Both PrP-sen and PrP-res are made up of the exact same string of amino acids, the building blocks that make up proteins. However, the two forms have different shapes.

PrP-sen is produced by normal healthy cells. The sen stands for “sensitive” because this version of the protein is sensitive to being broken down.

PrP-sen is present mainly in neurons in the brain, but is also found in other cell types.

Scientists don’t know the exact function of PrP-sen, but there is evidence that it may be involved in communication between neurons, cell death, and controlling sleep patterns. Interestingly, mice that are genetically engineered to produce no PrP-sen seem to be healthy.

The second type of prion protein, known as PrP-res, is the disease-causing form. Organisms with it develop spongiform disease. “res” stands for “resistant” because this version of PrP is resistant to being broken down.

Unlike other infectious agents, prions do not contain genetic material. However, once they infect an individual, prions can replicate. How is this possible?

Scientists are still working out the details, but evidence supports the idea that when PrP-sen comes into contact with PrP-res it is converted to PrP-res. The result is a chain reaction that multiplies copy after copy of the infectious prion.

Because of their abnormal shape, PrP-res proteins tend to stick to each other. Over time, the PrP-res molecules stack up to form long chains called “amyloid fibers”.

Amyloid fibers are toxic to cells, and ultimately kill them.

Cells called astrocytes crawl through the brain digesting the dead neurons, leaving holes where neurons used to be. The amyloid fibers remain.

Structure of Prion

The normal prion structure is characterized by four helices, denoted as PrPcThe abnormal one consist of 2 helices and 4 beta-sheets, which derived from the two helices of PrPc, is denoted as PrPse

Transmissible Spongiform Encephalopathies~Prion Disease

NORMAL ABNORMAL

-helix rich -sheet rich

PrPc PrPd

Chain-reaction Conversion of PrPc to PrPsc

PrPc PrPsc Chain-reaction Conversion

The harmful PrPSc form is very resistant to high temperatures, UV-irradiation and strong degradative enzymes.

How PrPsc attack the Brain?

Brain consists of a mass of nerve tissue (Hundred billions of neuron) and neuroglia, supporting neural tissue. When enough PrPSc proteins have been made they form long filamentous aggregates that gradually damage neuronal tissue.When neuron in the brain are all dead, the appearance of the brain will become sponge-like appearance. And this eventually lead to death.

Different prions affect different regions of the brain

Cerebral cortex: the symptoms include loss of memory and mental acuity, also visual imparement (CJD).

Thalamus: Fatal Familial Insomnia (FFI).

Cerebellum: lose the control of body movements and difficulties to walk (kuru, GSS).Brain stem: In the mad cow disease (BSE), the brain stem is affected.

TSEsT: Transmissible (Communicable)S: Spongiform (Look like sponge)E: Encephalopathy (Brain diseases)Prion diseases are often called

transmissible spongiform encephalopathies (TSE).Because after the infection, the brain appearance become a sponge-like apearance.

Six forms of TSEs:

1) CJD - Creutzfeld-Jacob Disease 2) BSEs -Bovine-Spongiform-

Encephalopathy 3) Alper's Syndrome

4) GSS - Gerstmann-Straussler-Scheinkner syndrome

5) FFI - Fatal Familial Insomnia

6) Kuru

Transmission Between Species

BSE SheepMinkDeer/ElkHumans

IC; POIC; POICPO

Scrapie CattleMinkDeer/ElkHumans

ICICIC

TME CattleSheepDeer/ElkHumans

ICIC

CWD CattleSheepMinkHumans

ICICIC

SOURCE → → → → → → HOST ROUTE

CJD - Creutzfeld-Jakob Disease

The disease causes fatal degradation of brain tissue and produces a dementia that affects men and women, often between the ages of 50 and 65.90% cases progress to death within a year

There is no record of anyone recovering from the disease and there is no known treatment.

Causes

CJD is associated with prions, mutated forms of a normal protein produced in nerve cells, white blood cells, muscle cells, and the cells of many other tissues.

Just how prions cause the disease symptoms remains unclear.

There are three types of the disease: sporadic, genetic, and iatrogenic.

The 3 Type of CJD

Sporatic CJD: Spontaneous mutation. 85% of the cases.

genetic CJD: a mutant prion gene is passed genetically from one generation to another. 10-15% of the cases.

Iatrogenic CJD: Contaminated directly to the brain (eg: Surgery)

New variant CJD: CJD with shorter incubation: a form of Creutzfeldt-Jakob disease that has a much shorter incubation period than previously recognized types but is clinically identical. It first appeared in the late 1980s.

BSEs: Bovine Spongiform encephalopathy

MAD COW DESEASE

How Cows

are

infected?

BSEWay of infection

The cow eat offal of the infected sheep

Prions are taken up from the gut and transported along nerve fibers to the brain stem.

Prions accumulate and convert normal prion proteins to the disease-causing form, PrPSc.

Years later, BSE results when a sufficient number of nerve cells have become damaged, affecting the behaviour of the cows. And eventually the cow is dead.

THE END&

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