Structure of Prion

The normal prion structure is characterized by four helices, denoted as PrPc

The abnormal one consist of 2 helices and 4 beta-sheets, which derived from the two helices of PrPc, is denoted as PrPse

Figure 1: Proposed three-dimensional structure (a) PrPC and (b) PrPSc

The Conversion of PrPc to PrPse

(a) (b)

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.

Prions infect animals & Humans…

What are the Prion-Related Diseases?

Are all known prion diseases fatal ? YES, they are.

& where Prion-Related Diseases Occur?

TSEsTSEs

T: 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

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

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.

Symptom

Bored with food, unsociable . No capability in memorizing anything.. Loss of control of the muscle movement. Can not speak and swallow the food.