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1. Introduction
2. Hundreds of thousands of cattle infected with BSE
3. The vCJD epidemic
4. New challenges
5. Identify source of infection
6. Defining the TSE strain: in vivo
7. Defining the TSE strain: in vitro
8. Understand host susceptibility
9. The prion hypothesis
10. Strategy
11. Targeting the PrP gene - step 1 in vitro
12. Targeting the PrP gene - step 2 in vivo
13. Targeting the murine PrP gene
14. PrP is required for TSE disease
15. PrnP gene dosage influences the incubation time
16. Human mutations and polymorphisms
17. Modelling susceptibility between species
18. Other factors controlling incubation time
19. Modelling human susceptibility to TSEs
20. vCJD transmission to transgenic mice
21. Transgenic mice infected with vCJD
22. Predicting the risk of transmission of vCJD
23. An amino acid alteration and host susceptibility (1)
24. An amino acid alteration and host susceptibility (2)
25. The 101L mutation decreases incubation time
26. Scrapie is an infectious disease, not a genetic one
27. PrP glycosylation and host susceptibility
28. PrP glycosylation deficient mice
29. Results in the absence of PrP glycosylation
30. Effect on incubation time in the absence of G2
31. G1 Absence provides resistance to ME7
32. Host PrP glycosylation deficient mice
33. Define routes of transmission to animals
34. Possible routes of transmission of vCJD
35. Modelling vCJD by blood transfusion in sheep
36. Advantages of using sheep
37. Initial experiments
38. Results
39. Transmission of vCJD by blood transfusion
40. Questions
41. Define transmission within animal
42. Transmission of TSE agent within a host
43. FDC depletion blocks oral scrapie transmission
44. The role of PrP expression
45. Inducible expression of PrP
46. Predicting host range of a TSE strain
47. Carriers of infection
48. vCJD risk of transmission in gene targetted mice
49. Prevalence of PrP in UK tissue samples
50. Diagnosis and co-located PrPSc and infectivity
51. Infectious brains with no abnormal forms of PrP
52. Abnormal PrP can accumulate without disease
53. Mouse inoculated with a human TSE disease
54. What is the role of PrP amyloid?
55. What is the role of PrPSc in disease?
56. Protein misfolding and infectivity
57. Key areas still to be addressed
58. Acknowledgements

Topics Covered

• The TSEs continue to pose a problem to animal and human health
• The vCJD epidemic appears to be in decline but new risks of human to human transmission are now apparent
• Chronic wasting disease is a major problem currently in the US although its presence has not yet been detected in Europe
• Predicting and preventing transmission of disease requires an understanding of the routes of transmission within and between animals and the host factors which determine susceptibility
• We have studied natural disease and both in vivo and in vitro model systems to unravel the basic mechanisms of disease
• PrP protein has a central role in the outcome disease and mutations and polymorphisms in host PrP can profoundly alter the host's susceptibility to a TSE agent
• Precisely how host PrP influences the outcome of disease has not been established
• Both mutations and glycosylation can profoundly influence transmission both within and between species

Links

Series:

• Prions and Amyloids

Categories:

• Clinical Practice
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on October 22, 2008
• Archived on February 25, 2021

Financial Disclosures

• Prof. Jean Manson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.