Selasa, 21 Ogos 2012

Prion Disease

Prion Disease

Based on textbook of biochemistry :

- It is a neurodegenerative disorder disease.

- Can affect both human and animal.

- Referred as Transmissible Spongiform Encephalopathies ( mad cow disease ).

- Some symptoms :

* Dementia - a chronic and progressive deterioration of behaviour and higher intellectual function due to organic brain disease.

* Loss of coordination.

- Prion Protein is a normal constituent of brain tissue in all mammals.

* present on the surface of neuron and glial cells.

* its role is unknown in detail. But, it appears to have a molecular signalling function.

- PrP ( Prion Protein )

* become infectious when it changes in 3-dementional conformation.

* a number of Alpha-helices in non-infectious PrP are replaced by Beta-sheets in the infectious form.

- Infectious PrP, act as template.

* Because, for converting the normal PrP to the infectious conformation.

* Tend to form insoluble aggregates of fibrils similar to the amyloid found in neurodegenerative disorder.

* These aggregates, damage or destroy nerve cells and create microscopic sponge-like hole in the brain.

Something from wikipedia :

Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloid, which disrupt the normal tissue structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons.

 Other histological changes include astrogliosis and the absence of an inflammatory reaction.While the incubation period for prion diseases is generally quite long[vague], once symptoms appear the disease progresses rapidly, leading to brain damage and death. Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes.

*Convulsion - an involuntary contraction of the muscles producing contortion of the body and limbs.

All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal. A vaccine has been developed in mice, however, that may provide insight into providing a vaccine in humans to resist prion infections. Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production – thus theoretically making them immune to BSE, building on research indicating that mice lacking normally occurring prion protein are resistant to infection by scrapie prion protein.

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals. Due to small differences in PrP between different species it is unusual for a prion disease to be transmitted from one species to another. The human prion disease variant Creutzfeldt-Jakob disease, however, is believed to be caused by a prion which typically infects cattle, causing Bovine spongiform encephalopathy and is transmitted through infected meat.


It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic. It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.

Current research suggests that the primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.

A University of California research team, led by Nobel Prize winner Stanley Prusiner, has provided evidence for the theory that infection can occur from prions in manure. And since manure is present in many areas surrounding water reservoirs, as well as used on many crop fields, it raises the possibility of widespread transmission. It was reported in January 2011 that researchers had discovered prions spreading through airborne transmission on aerosol particles, in an animal testing experiment focusing on scrapie infection in laboratory mice.

 Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived human menopausal gonadotropin, administered for the treatment of infertility, was published in 2011.


Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions therefore involves the denaturation of the protein to a state where the molecule is no longer able to induce the abnormal folding of normal proteins. Prions are generally quite resistant to proteases, heat, radiation, and formalin treatments, although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein hydrolysis or reduction or destruction of protein tertiary structure.

Examples include bleach, caustic soda, and strongly acidic detergents such as LpH.134°C (274°F) for 18 minutes in a pressurized steam autoclave may not be enough to deactivate the agent of disease. Ozone sterilization is currently being studied as a potential method for prion denature and deactivation. Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions.

The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:

Immerse in a pan containing 1N NaOH and heat in a gravity-displacement autoclave at 121°C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes.

Immerse in 1N NaOH or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121°C for 1 hour; clean; and then perform routine sterilization processes.

Immerse in 1N NaOH or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121°C) or in a porous-load (134°C) autoclave for 1 hour; clean; and then perform routine sterilization processes.

From Genetics Home Refence :

 What is prion disease?

Prion diseases belong to group of progressive conditions that affect the nervous system in humans and animals. In people, prion diseases impair brain function, causing memory changes, personality changes, a decline in intellectual function (dementia), and problems with movement that worsen over time. The signs and symptoms of these conditions typically begin in adulthood, and these disorders lead to death within a few months to several years.

Familial prion diseases of humans include classic Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal insomnia (FI). These conditions form a spectrum of diseases with overlapping signs and symptoms.

How common is prion disease?

These disorders are very rare. They affect about one person per million worldwide each year. Approximately 300 cases occur annually in the United States.

What genes are related to prion disease?

Mutations in the PRNP gene cause prion disease.
Only a small percentage of prion disease cases run in families. Most cases are sporadic, which means they occur in people without any known risk factors or gene mutations. Rarely, prion diseases can be transmitted by accidental exposure to prion-contaminated tissues during a medical procedure. This type of prion disease is called iatrogenic.

One type of prion disease in humans, variant Creutzfeldt-Jakob disease (vCJD), is acquired by eating beef products obtained from cattle with prion disease. In cows, this form of the disease is known as bovine spongiform encephalopathy (BSE) or, more commonly, "mad cow" disease. Another example of an acquired human prion disease is kuru, which was identified in the South Fore tribe in Papua New Guinea. The disorder was transmitted when tribe members ate the tissue of affected people during cannibalistic funeral rituals.

Familial forms of prion disease are caused by inherited mutations in the PRNP gene. This gene provides instructions for making a protein called prion protein (PrP). Normally, this protein is likely involved in transporting copper into cells. It may also play a role in protecting brain cells and helping them communicate. In familial cases of prion disease, mutations in the PRNP gene cause cells to produce an abnormal form of the prion protein known as PrPSc. In iatrogenic and acquired cases, an affected person develops prion disease from exposure to this abnormal protein.

In a process that is not fully understood, PrPSc has the ability to convert the normal prion protein, PrPC, into more PrPSc. This abnormal protein builds up in the brain, forming clumps that damage or destroy nerve cells. The loss of these cells creates microscopic sponge-like holes in the brain, which leads to the signs and symptoms of prion disease.

How do people inherit prion disease?

Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene.

Although such people most likely do not have an affected parent, they can pass the genetic change to their children.

The sporadic, iatrogenic, and acquired forms of prion disease, including kuru and variant Creutzfeldt-Jakob disease, are not inherited.

What other names do people use for prion disease?

-Inherited Human Transmissible Spongiform Encephalopathies
-Prion-associated disorders
-Prion-Induced Disorders
-Prion Protein Diseases
-Transmissible Dementias
-Transmissible Spongiform Encephalopathies

-Mr Hope-


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