Spongiform Encephalopathies ( TSEs)

1. Spongiform Encephalopathies(TSEs)

2. Transmissible spongiform encephalopathies • Transmissible spongiform encephalopathies (TSEs) are a family of diseases of humans and animals. • They are transmitted by prions, but other suggest an involvement of a Spiroplasma infection. • Characterized by spongy degeneration of the brain with severe and fatal neurological signs and symptoms. • Including memory changes, personality changes and problems with movement that worsen over time.

3. The spongiform encephalopathies include the following: http://www.antisel.gr/msp/Prion%20diseases_introduction.htm

4. PrionProtein and TSEs • The mis-folded form of the prion protein has been implicated in a number of diseases in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle and Creutzfeldt-Jakob disease (CJD) in humans. • The infectious agent in TSEs is a specific protein called prion protein. Misshaped prion proteins carry the disease between individuals and cause deterioration of the brain.

5. Features of TSE The degenerative tissue damage caused by human prion diseases is characterised by four features: • spongiform change, • neuronal loss, • astrocytosis • Amyloid plaque formation. http://en.wikipedia.org/wiki/Image:Aphis.usda.gov_BSE_5.jpg

6. Clinical signs in humans • The clinical signs in humans vary • commonly include personality changes • psychiatric problems such as depression, • lack of coordination or an unsteady gait (ataxia). • Patients also may experience involuntary jerking movements called myoclonus, • unusual sensations • insomnia • Confusion or memory problems. In the later stages of the disease: • patients have severe mental impairment (dementia) • lose the ability to move or speak.

7. Genetics • Mutations in the PRNP gene cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene • Change in codon 102 from proline to leucine in the prion protein gene (PRNP) causes Gerstmann-Sträussler-Scheinker syndrome. • asparagine-178 replaces aspartic acid while methionine is present at amino acid 129.(Fatal familial insomnia) • Only a small percentage of all cases of prion disease run in families • Rarely, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease.

8. Functions of Prion protein (PrP) • The PRNP gene provides the instructions to make a protein called the prion protein (PrP) • Normally, this protein may be involved in transporting copper into cells • It may also be involved in protecting brain cells and helping them communicate. • 24 Point-Mutations in this gene cause cells to produce an abnormal form of the prion protein, known as PrPSc. • This abnormal protein builds up in the brain and destroys nerve cells.

9. Familial forms of prion disease • Familial forms of prion disease are inherited in an autosomal dominant pattern • 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.

10. Bovine spongiform encephalopathy (BSE) • BSE is a transmissible, neuro-degenerative fatal brain disease of cattle. • The disease has a long incubation period of 4-5 years and it is fatal for cattle within weeks to months of its onset. The nature of the BSE agent is still being debated. • Strong evidence currently available supports the theory that the agent is composed largely, if not entirely, of a self-replicating protein, referred to as a prion. • It is transmitted through the consumption of BSE-contaminated meat and bone meal supplements in cattle feed.

11. What causes the epidemic? • The epidemic was caused by cattle, who are normally herbivores, being fed the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread. • The origin of the disease itself remains unknown. • The infectious agent is distinctive for the high temperatures at which it remains. • Another contributory factor was the feeding of infected protein supplements to very young calves.

12. Prion protein in BSE • The infectious agent in BSE is believed to be a specific type of misfoldedprotein called a prion. • The same type of prion protein gene mutation as found in human patients with the genetic form of Creutzfeldt-Jakob disease, also called genetic CJD • Those prion proteins carry the disease between individuals and cause deterioration of the brain. • BSE is a type of transmissible spongiform encephalopathy (TSE). • TSEs can arise in animals that carry an allele which causes previously normal protein molecules to contort by themselves from an alpha helical arrangement to a beta pleated sheet, which is the disease-causing shape for the particular protein

13. Proposed mechanism of prionpropagation http://en.wikipedia.org/wiki/Image:Prion_propagation.png

14. Transmission of BSE • Transmission can occur when healthy animals come in contact with tainted tissues from others with the disease. • In the brain these proteins cause native cellular prion protein to deform into the infectious state, which then goes on to deform further prion protein in an exponential cascade. • This results in protein aggregates, which then form dense plaque fibers, leading to the microscopic appearance of "holes" in the brain, degeneration of physical and mental abilities, and ultimately death. http://www.antisel.gr/msp/Prion%20diseases_Prion.htm

15. Transmission to humans • It is believed by most scientists that the disease may be transmitted to human beings who eat the brain or spinal cord of infected carcasses. • In humans, it is known as new variant Creutzfeldt-Jakob disease (vCJD or nvCJD http://en.wikipedia.org/wiki/Image:Aphis.usda.gov_BSE_3.jpg

16. References • http://www.who.int/zoonoses/diseases/bse/en/ • http://www.specialeducation.gr/modules.php?op=modload&name=News&file=article&sid=110 • http://www.plospathogens.org/article/info:doi%2F10.1371%2Fjournal.ppat.1000206 • http://agr.wa.gov/FoodAnimal/AnimalFeed/BSE.htm • http://en.wikipedia.org/wiki/Fatal_familial_insomnia • http://www.who.int/zoonoses/diseases/bse/en/ • http://en.wikipedia.org/wiki/Transmissible_spongiform_encephalopathy • http://www.medlook.net/category.asp?category=101 • http://www.kepka.org/Grk/info/Nutricion/nut003_019.htm