General Background on Prions

1. General Background on Prions

2. 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).

3. Discovery • Study started in 1967 by British scientist, Tikvah Alper, at Hammersmith Hospital in London. • Discovered by American neurologist, Stanley B. Prusiner, in 1982.

4. Where are prions? • Proteins on the cell membrane of neurons of the brain in mammals • Normal prion protein is noted as PrPC • Mutated prion protein is noted as PrPSC • The secondary structure of the prion protein seems to be affected.

5. Basic Structure • Normal prions contain about 200-250 amino acids twisted into three telephone chord-like coils known as helices, with tails of more amino acids.

6. Basic Structure • Normal prions contain about 200-250 amino acids twisted into three telephone chord-like coils known as helices, with tails of more amino acids. • The mutated, and infectious, form is built from the same amino acids but take a different shape. Normal Mutated

7. Basic Structure • Normal prions contain about 200-250 amino acids twisted into three telephone chord-like coils known as helices, with tails of more amino acids. • 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

8. Basic Structure Normal Mutated

9. Differences From Bactera & Viruses • Prions do not contain nucleic acid; they don’t have DNA or RNA.

10. Differences From Bactera & Viruses • Prions do not contain nucleic acid; they don’t have DNA or RNA. • They are extremely resistant to heat and chemicals.

11. Differences From Bactera & 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.

12. Prion Diseases • Humans: CJD (Creutzfeldt Jakob Disease) GSS (Gerstmann Straussler Syndrome)

14. Symptoms of prion disease in humans • Rapidly developing dementia • Difficulty walking and changes in gait • Hallucinations • Muscle stiffness • Confusion • Fatigue • Difficulty speaking

15. How Prion disease is diagnosed • MRI scans of the brain • Samples of fluid from the spinal cord (spinal tap) • Electroencephalogram, which analyzes brain waves; this painless test requires placing electrodes on the scalp • Blood tests • Neurologic and visual examinations to evaluate for nerve damage and vision loss

16. Neurodegenerative disease experts have long been concerned that prion diseases might be transmitted through the transfusion of blood products. • Although cross-species transmission between cows and humans of the disease is relatively difficult, inter-species transmission between humans through blood transfusion is efficient and if unmanaged, could pose a serious risk. This is particularly worrying since prion diseases typically have very long silent incubation periods, sometimes extending over many decades, and at present there is no reliable blood test to screen for the presence of the infectious prion agent. Lancet paper: vCJD case report 14 December 2006

17. Prevention of Prion disease on humans • Properly sterilizing medical equipment may prevent the spread of the disease. If you have or may have CJD, you should not donate organs or tissue, including corneal tissue. Newer regulations that govern the handling and feeding of cows may help prevent the spread of prion diseases.

18. Prion Diseases • Humans: CJD (Creutzfeldt Jakob Disease) GSS (Gerstmann Straussler Syndrome) • Cattle: BSE (Bovine Spongiform Encephalopathy, better known as Mad Cow Disease)

19. Prion Diseases • Humans: CJD (Creutzfeldt Jakob Disease) GSS (Gerstmann Straussler Syndrome) • Cattle: BSE (Bovine Spongiform Encephalopathy, better known as Mad Cow Disease) • Sheep: Scrapie • Deer/Elk: CDW (Chronic Wasting Disease)

20. Figure 1. Histopathology showing spongiform degeneration and astrocytic gliosis (adapted from the Prion Group at the University of Duesseldorf )

21. Vaccine? • The development of a vaccine against the infectious form of prions has proven to be unsuccessful due to the lack of innate or antigen-induced immune response against the host-encoded protein.

22. Controversy • DNA and RNA are the only substances now known to replicate in body tissues, so how do prions make copies of themselves without any nucleic acids?

23. Controversy • DNA and RNA are the only substances now known to replicate in body tissues, so how do prions make copies of themselves without any nucleic acids? • Some believe TSEs are caused by an unidentified slow-acting virus. • Others believe a small virus accompanies a prion and they work together to cause disease.

24. One proposed method for prion replication Note that normal PrPC is onvolved in replication of mutated PrPSc

26. References • www.hartnell.cc.ca.us/faculty/jhodin/Group9.ppt • http://www.scq.ubc.ca/prions-infectious-proteins-repsonsible-for-mad-cow-disease/ • http://www.hopkinsmedicine.org/healthlibrary/conditions/nervous_system_disorders/prion_diseases_134,56/ • http://prion.systemsbiology.net/page/PosterView/display/poster_id/13 • http://www.ucl.ac.uk/news/news-articles/0612/06121401